基于食物過敏的傣藥“雅解沙把”解“食物毒”作用機(jī)制研究
發(fā)布時(shí)間：2018-09-08 18:55
【摘要】：目的傣醫(yī)解"食物毒"是"雅解"理論的重要組成部分,近年來,在"雅解"理論指導(dǎo)下的解"食物毒"及其方藥一直是傣醫(yī)藥領(lǐng)域研究的重點(diǎn)和熱點(diǎn)。研究發(fā)現(xiàn)"食物毒"與食物過敏密切相關(guān);"雅解沙把"是解"食物毒"方藥之一,臨床觀察及實(shí)驗(yàn)研究均證實(shí)其有較好的解"食物毒"作用,但目前研究尚不能全面揭示其解"食物毒"作用機(jī)理。故在前期研究的基礎(chǔ)上,本研究擬達(dá)到以下目的:1運(yùn)用統(tǒng)計(jì)學(xué)方法對傣醫(yī)解"食物毒"單、驗(yàn)方的規(guī)律進(jìn)行分析,以期證實(shí)傣醫(yī)"食物毒"與食物過敏有相關(guān)性,食物過敏是最能體現(xiàn)"食物毒"內(nèi)涵的疾病之一;"雅解沙把"是解"食物毒"代表方;腸道是研究解"食物毒"的角度或途徑,從而為開展實(shí)驗(yàn)研究及臨床運(yùn)用提供依據(jù)。2根據(jù)上述理論研究,基于食物過敏小鼠模型,從腸黏膜屏障的生物屏障、物理屏障、免疫屏障為切入點(diǎn)研究傣藥"雅解沙把"抗食物過敏可能的作用機(jī)制,從而揭示其解"食物毒"的作用機(jī)制。方法1理論研究運(yùn)用文獻(xiàn)分析法收集解"食物毒"相關(guān)"雅解"單方、驗(yàn)方,并進(jìn)行規(guī)范化整理。運(yùn)用頻數(shù)分析法對其使用的藥物進(jìn)行統(tǒng)計(jì)分析,分析總結(jié)其類別、性、味、歸塔,主治類別、主治范圍及主治癥狀等方面的頻數(shù)結(jié)構(gòu)及分布情況。在對藥物進(jìn)行頻數(shù)分析的基礎(chǔ)上,運(yùn)用聚類分析法對藥物類別進(jìn)行聚類分析。2實(shí)驗(yàn)研究2.1復(fù)制卵清蛋白過敏小鼠模型40只BALB/c雌鼠,6-8周齡,隨機(jī)分為正常對照組、OVA模型組、"雅解沙把"低劑量組(0.39g/kg)、"雅解沙把"中劑量組(1.17g/kg)、"雅解沙把"高劑量組(3.51g/kg)。小鼠于實(shí)驗(yàn)第0天腹腔注射致敏液(10μgOVA加1mg氫氧化鋁),第14天腹腔注射致敏液(含10μgOVA),第30天、34天灌胃致敏液(含80mgOVA)。正常對照組用超純水代替進(jìn)行致敏和激發(fā)。2.2藥物干預(yù)實(shí)驗(yàn)在實(shí)驗(yàn)第30天-34天予OVA灌胃激發(fā)前1小時(shí),對藥物干預(yù)組小鼠以灌胃方式給予"雅解沙把"低、中、高劑量治療;正常對照組和模型組小鼠以灌胃方式給予生理鹽水治療,共5天。2.3 卵清蛋白過敏模型評價(jià)指標(biāo)檢測在兩次OVA灌胃激發(fā)后1小時(shí)內(nèi),觀察各組小鼠過敏癥狀、腹瀉情況。在末次OVA灌胃激發(fā)1小時(shí)后,取血清標(biāo)本,采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA)檢測特異性O(shè)VA-IgE水平。2.4 腸道菌群結(jié)構(gòu)檢測實(shí)驗(yàn)?zāi)┤⌒∈蠹S便液氮中凍存,利用Illumina高通量測序平臺對各組小鼠糞便標(biāo)本中的16S rRNA gene V3-V4區(qū)進(jìn)行定性分析,探索小鼠腸道菌群結(jié)構(gòu)的變化。2.5 腸黏膜通透性檢測采用熒光定量PCR方法檢測小鼠空腸緊密連接蛋白Occludin mRNA、Claudin 3 mRNA的含量。2.6 腸黏膜免疫檢測采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA)檢測血清IL-4、IFN-γ、IL-4/IFN-γ及小鼠腸黏膜sIgA水平;熒光定量PCR方法檢測小鼠空腸IL-17、TGF-β1、TGF-β1/IL-17mRNA的含量。結(jié)果1 解"食物毒"方藥物規(guī)律分析解"食物毒"相關(guān)方藥物中,共收集到57首258味次、115味單方、驗(yàn)方。通過頻次分析得出,藥物類別以解藥類為主,占45.74%;藥物使用頻率超過或等于2次的藥物共計(jì)48味、占總味數(shù)的41.74%;藥性主要以涼、寒為主,占比分別為:40.31%和20.54%;藥味主要以苦味為主,占45.35%;藥物入塔主要以風(fēng)塔為主,占29.20%。"食物毒"類別以誤食毒物及食物中毒為主,占35.27%和31.40%;主治范圍以消化系統(tǒng)為主,占54.64%。主治癥狀主要以腹瀉、嘔吐為主,各占18.06%。通過頻數(shù)分析與聚類分析,解"食物毒"藥物可歸為7類藥物組合方,其中相類方"雅解沙把"符合安全性、可操作性、可獲取性等臨床應(yīng)用推廣條件。2 卵清蛋白過敏小鼠模型評價(jià)指標(biāo)結(jié)果2.1 過敏癥狀第一次OVA灌胃激發(fā)后,"雅解沙把"低、中、高劑量組小鼠過敏癥狀分?jǐn)?shù)較模型組均降低,但差異無統(tǒng)計(jì)學(xué)意義(P0.05)。第二次OVA灌胃激發(fā)后,"雅解沙把"低、中、高劑量組小鼠過敏癥狀分?jǐn)?shù)較模型組明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。2.2腹瀉癥狀第一次OVA灌胃激發(fā)后,"雅解沙把"低、中、高劑量組小鼠腹瀉分?jǐn)?shù)較模型組均降低,但只有中劑量組有顯著性差異(P0.05)。第二次OVA灌胃激發(fā)后,藥物干預(yù)組小鼠腹瀉分?jǐn)?shù)較模型組均明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。2.3血清OVA-IgE水平藥物干預(yù)組小鼠血清OVA-IgE水平較模型組均降低,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。3腸道菌群結(jié)構(gòu)結(jié)果3.1小鼠糞便菌群Alpha多樣性及和豐富度藥物干預(yù)組小鼠腸道總微生物群落豐度指標(biāo)ACE、Chao1指數(shù)較模型組無差異(P0.05),但"雅解沙把"高劑量有增加兩者的趨勢。同時(shí)藥物干預(yù)組小鼠Shannon指數(shù)較模型組有升高趨勢;而Simpson指數(shù)有下降趨勢,但只有中劑量組有統(tǒng)計(jì)學(xué)意義(P0.05)。3.2小鼠腸道微生態(tài)構(gòu)成及分布豐度在"門"水平上,與模型組相比,藥物干預(yù)組小鼠厚壁菌門細(xì)菌比例呈減少趨勢,以高劑量組明顯,差異有統(tǒng)計(jì)學(xué)意義(P0.05);而擬桿菌門細(xì)菌比例呈增加趨勢,以高劑量組明顯,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在"屬" 水平上,與模型組相比,乳酸桿菌(Lactobacillus)屬細(xì)菌呈減少趨勢,但差異無統(tǒng)計(jì)學(xué)意義(P0.05);而Barnesiella屬細(xì)菌呈增加趨勢,以高劑量顯著,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。3.3腸道微生物群落結(jié)構(gòu)差別與模型組相比,藥物干預(yù)組小鼠微生物群落樣品在空間分布上相對獨(dú)立,能明顯分開。4腸黏膜通透性結(jié)果與模型組相比,藥物干預(yù)組小鼠腸上皮緊密連接蛋白Occludin mRNA表達(dá)量明顯增高,差異均有統(tǒng)計(jì)學(xué)意義(P0.05);而腸上皮緊密連接蛋白Claudin3mRNA表達(dá)量無明顯變化,無統(tǒng)計(jì)學(xué)意義(P0.05)。5腸黏膜免疫結(jié)果與模型組相比,"雅解沙把"低、中劑量組小鼠血清IL-4濃度有升高趨勢,但無統(tǒng)計(jì)學(xué)差異(P0.05),而"雅解沙把"高劑量組小鼠血清IL-4濃度明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。與模型組相比,藥物干預(yù)組小鼠血清IFN-γ濃度明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。藥物干預(yù)組均有下調(diào)小鼠血清IL-4/IFN-γ比值的趨勢,但只有高劑量比值顯著降低,差異統(tǒng)計(jì)學(xué)意義(P0.05)。與模型組相比,藥物干預(yù)組小鼠IL-17mRNA表達(dá)量、TGF-β1mRNA表達(dá)量、TGF-β1/IL-17比值及sIgA水平均無差異(P0.05)。結(jié)論1 解"食物毒"方藥規(guī)律以解藥類藥物為主;藥性以涼為主,藥味以苦味為主;配伍以復(fù)方為主,遵循寒熱并用,調(diào)平"四塔"原則。2 傣醫(yī)部分"食物毒"與食物過敏有相關(guān)性,食物過敏是最能體現(xiàn)"食物毒"內(nèi)涵的疾病之一。"雅解沙把"是解"食物毒"代表方之一,腸道是研究的角度和途徑,腹瀉是"食物毒"的主要癥狀之一。3 "雅解沙把"通過降低過敏癥狀分?jǐn)?shù)、腹瀉分?jǐn)?shù)、血清OVA-IgE水平,緩解卵清蛋白過敏小鼠癥狀。4 "雅解沙把"通過升高小鼠Shannon指數(shù),降低Simpson指數(shù),增加菌落多樣性,調(diào)節(jié)失衡的腸道菌群。5 在腸道微生態(tài)的門水平上,"雅解沙把"能降低小鼠厚壁菌門細(xì)菌比例,增加擬桿菌門細(xì)菌比例,恢復(fù)失衡的腸道菌群,且以"雅解沙把"高劑量效果顯著。6 在腸道微生態(tài)的屬水平上,"雅解沙把"能降低小鼠乳酸桿菌屬細(xì)菌比例,增加Barnesiella屬細(xì)菌比例,恢復(fù)失衡的腸道菌群,且以"雅解沙把"高劑量效果顯著。7 "雅解沙把"可以恢復(fù)小鼠腸道微生物群落結(jié)構(gòu)差別。8 "雅解沙把"通過提高小鼠Occludin mRNA的含量,保護(hù)腸黏膜上皮的完整性,降低通透性,其對Claudin 3 mRNA的含量無影響。9 "雅解沙把"通過降低小鼠血清IL-4濃度,升高IFN-γ濃度,下調(diào)IL-4/IFN-γ比值,可對免疫細(xì)胞Th2優(yōu)勢所致的免疫失衡狀態(tài)進(jìn)行調(diào)節(jié),恢復(fù)Th1/Th2平衡。10 "雅解沙把"對 IL-17 mRNA、TGF-β1 mRNA 表達(dá)量,TGF-β1/IL-17 比值及 sIgA水平無影響。11 "雅解沙把"治療食物過敏具有應(yīng)用前景,尤其是高劑量效果顯著。
[Abstract]:OBJECTIVE To understand food poisoning in Dai medicine is an important part of Yajie theory. In recent years, it has been the focus and hotspot in the field of Dai medicine to solve food poisoning and its prescriptions under the guidance of Yajie theory. It has been proved that it has a good effect on "food poisoning", but the mechanism of "food poisoning" can not be fully revealed in the present study. Therefore, on the basis of previous studies, this study intends to achieve the following purposes: 1. Using statistical methods to analyze the rules of Dai medicine's "food poisoning" list and prescriptions, in order to confirm the Dai medicine's "food poisoning" and food allergy. Relatively, food allergy is one of the diseases that can best reflect the connotation of "food toxicity"; Yajiesha Ba is the representative prescription of "food toxicity"; intestinal tract is the angle or way to study the understanding of "food toxicity", so as to provide the basis for experimental research and clinical application. Object barrier, physical barrier, immune barrier as the breakthrough point to study the possible mechanism of Dai medicine "Yajieshaba" anti-food allergy, so as to reveal the mechanism of its anti-food toxicity. Methods 1 Theoretical research using literature analysis method to collect the "Yajie" related to "food toxicity" single, test prescriptions, and standardize. The frequency structure and distribution of the drugs were analyzed and summarized in terms of category, sex, taste, attribution, main treatment category, main treatment range and main symptoms. 0 female BALB/c mice aged 6-8 weeks were randomly divided into normal control group, OVA model group, low dose group (0.39 g/kg), middle dose group (1.17 g/kg) and high dose group (3.51 g/kg). The mice were intraperitoneally injected with sensitizing solution (10 mg OVA plus 1 mg aluminium hydroxide) on day 0, day 14 and day 30 respectively. The normal control group was given super pure water instead of sensitizing and stimulating. 2.2 Drug intervention experiment was given OVA 1 hour before stimulating by gavage on the 30th and 34th days of the experiment. The mice in the drug intervention group were given Yajieshabao by gavage at low, medium and high doses; the mice in the normal control group and the model group were given Yajieshabao by gavage. The allergic symptoms and diarrhea of mice in each group were observed within 1 hour after two stimulations of OVA. After the last stimulation of OVA, serum samples were taken and the specific OVA-IgE level was detected by enzyme linked immunosorbent assay (ELISA). The 16S rRNA gene V3-V4 region was analyzed qualitatively by Illumina high-throughput sequencing platform to explore the changes of intestinal flora structure in mice. 2.5 Intestinal mucosal permeability was detected by fluorescence quantitative PCR to detect the tight junction protein Occludin m in mouse jejunum. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum IL-4, IFN-gamma, IL-4/IFN-gamma and sIgA in mouse intestinal mucosa; fluorescence quantitative PCR was used to detect the contents of IL-17, TGF-beta 1, TGF-beta 1/IL-17 mRNA in mouse jejunum. Among the prescriptions, 57 258 were collected, 115 were single, and the prescriptions were tested. Through frequency analysis, it was concluded that antidotes were the main types of drugs, accounting for 45.74%; 48 drugs were used more frequently than or equal to two times, accounting for 41.74%; medicinal properties were mainly cold, accounting for 40.31% and 20.54% respectively; bitterness was the main flavor. The main types of food poisoning were mistaken poisons and food poisoning, accounting for 35.27% and 31.40%; the main treatment areas were digestive system, accounting for 54.64%. The main symptoms were diarrhea and vomiting, accounting for 18.06% respectively. 2. Evaluation index of ovalbumin allergic mice model 2. 1 Allergic symptoms after the first OVA stimulation, the "Yajieshaba" was low, the middle and high dose group of mice allergic symptoms were lower than the model group, but the difference was not unified. The scores of allergic symptoms in the middle and high dose groups were significantly lower than those in the model group (P 0.01). 2.2 After the first OVA stimulation of diarrhea symptoms, the scores of diarrhea in the middle and high dose groups were lower than those in the model group, but only in the middle dose group. There was a significant difference between the two groups (P 0.05). After the second OVA stimulation, the diarrhea fraction of the drug intervention group was significantly lower than that of the model group (P 0.01). 2.3 The serum OVA-IgE level of the drug intervention group was significantly lower than that of the model group (P 0.05). 3 The intestinal flora structure of the drug intervention group was significantly lower than that of the model group (P 0.05). The diversity and richness of Alpha microflora in feces of mice were similar to those of the model group (P 0.05), but the high dosage of Yajieshabao increased both of them. But only the middle dose group had statistical significance (P 0.05). 3.2 mice intestinal microecological composition and distribution of abundance in the "gate" level, compared with the model group, the drug intervention group mice sclerenchyma bacterial proportion showed a decreasing trend, the high dose group was obvious, the difference was statistically significant (P 0.05); and the proportion of Bacteroides bacteria showed an increasing trend, with high dose. There was significant difference between the two groups (P 0.05). Compared with the model group, the number of Lactobacillus bacteria decreased, but the difference was not statistically significant (P 0.05), while the number of Barnesiella bacteria increased, with significant difference in high dose (P 0.05). Compared with the model group, the intestinal mucosal permeability of the drug intervention group was significantly higher than that of the model group, and the expression of Occludin mRNA in the intestinal epithelium of the drug intervention group was significantly higher than that of the model group (P 0.05). There was no significant difference in the expression of in3 mRNA between the two groups (P 0.05). 5 Compared with the model group, the immunological results of intestinal mucosa were lower. The serum IL-4 concentration of the middle dose group was higher, but there was no significant difference (P 0.05). The serum IL-4 concentration of the high dose group was significantly lower than that of the model group (P 0.05). Compared with the model group, the serum IFN-gamma concentration of the drug intervention group was significantly higher, the difference was statistically significant (P 0.01). The drug intervention group had a tendency to lower the serum IL-4/IFN-gamma ratio, but only the high dose ratio was significantly lower (P 0.05). Compared with the model group, the expression of IL-17 mRNA and TGF-beta 1 mRNA in the drug intervention group were significantly lower. There was no significant difference in the expression of TGF-1/IL-17 and sIgA levels (P 0.05). Conclusion 1 The antidote drugs were the main prescriptions for "food poisoning"; the main medicinal properties were cooling, and the main flavor was bitterness; the main compatibility was compound prescriptions, followed the principle of "four towers" and "cold and heat" were balanced. "Yajieshaba" is one of the representative prescriptions of "food poisoning". Intestinal tract is the angle and way of study. Diarrhea is one of the main symptoms of "food poisoning". 3 "Yajieshaba" alleviates the symptoms of ovalbumin-allergic mice by reducing the allergic symptoms, diarrhea, serum OVA-IgE levels. Over-elevating Shannon index, reducing Simpson index, increasing colony diversity and regulating the imbalance of intestinal flora. 5 At the gate level of intestinal microecology, "Yajiesha Bag" can reduce the proportion of sclerenchyma bacteria in mice, increase the proportion of Bacteroides bacteria, restore the imbalance of intestinal flora, and the high dose of "Yajiesha Bat" has a significant effect in the intestine. At the genus level of Tao micro-ecology, Yajieshaba could reduce the proportion of Lactobacillus, increase the proportion of Barnesiella, restore the unbalanced intestinal flora, and the effect of high dose Yajieshaba was significant. 7 Yajieshaba could restore the difference of intestinal microbial community structure in mice. 8 Yajieshaba could increase the Occludin of mice by increasing the proportion of Barnesiella. The content of mRNA, the integrity of intestinal mucosa epithelium and the permeability of intestinal mucosa were protected, but the content of Claudin 3 mRNA was not affected. 9 "Yajieshabao" could regulate the immune imbalance caused by Th2 dominance of immune cells and restore the Th1/Th2 balance by lowering serum IL-4 concentration, increasing IFN-gamma concentration and decreasing the ratio of IL-4 to IFN-gamma in mice. "No effect on the expression of IL-17 mRNA, TGF-beta 1 mRNA, TGF-beta 1/IL-17 ratio and sIgA level was observed. 11" Yajiesha "has a bright future in the treatment of food allergy, especially in high dosage.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R29
本文編號：2231396
[Abstract]:OBJECTIVE To understand food poisoning in Dai medicine is an important part of Yajie theory. In recent years, it has been the focus and hotspot in the field of Dai medicine to solve food poisoning and its prescriptions under the guidance of Yajie theory. It has been proved that it has a good effect on "food poisoning", but the mechanism of "food poisoning" can not be fully revealed in the present study. Therefore, on the basis of previous studies, this study intends to achieve the following purposes: 1. Using statistical methods to analyze the rules of Dai medicine's "food poisoning" list and prescriptions, in order to confirm the Dai medicine's "food poisoning" and food allergy. Relatively, food allergy is one of the diseases that can best reflect the connotation of "food toxicity"; Yajiesha Ba is the representative prescription of "food toxicity"; intestinal tract is the angle or way to study the understanding of "food toxicity", so as to provide the basis for experimental research and clinical application. Object barrier, physical barrier, immune barrier as the breakthrough point to study the possible mechanism of Dai medicine "Yajieshaba" anti-food allergy, so as to reveal the mechanism of its anti-food toxicity. Methods 1 Theoretical research using literature analysis method to collect the "Yajie" related to "food toxicity" single, test prescriptions, and standardize. The frequency structure and distribution of the drugs were analyzed and summarized in terms of category, sex, taste, attribution, main treatment category, main treatment range and main symptoms. 0 female BALB/c mice aged 6-8 weeks were randomly divided into normal control group, OVA model group, low dose group (0.39 g/kg), middle dose group (1.17 g/kg) and high dose group (3.51 g/kg). The mice were intraperitoneally injected with sensitizing solution (10 mg OVA plus 1 mg aluminium hydroxide) on day 0, day 14 and day 30 respectively. The normal control group was given super pure water instead of sensitizing and stimulating. 2.2 Drug intervention experiment was given OVA 1 hour before stimulating by gavage on the 30th and 34th days of the experiment. The mice in the drug intervention group were given Yajieshabao by gavage at low, medium and high doses; the mice in the normal control group and the model group were given Yajieshabao by gavage. The allergic symptoms and diarrhea of mice in each group were observed within 1 hour after two stimulations of OVA. After the last stimulation of OVA, serum samples were taken and the specific OVA-IgE level was detected by enzyme linked immunosorbent assay (ELISA). The 16S rRNA gene V3-V4 region was analyzed qualitatively by Illumina high-throughput sequencing platform to explore the changes of intestinal flora structure in mice. 2.5 Intestinal mucosal permeability was detected by fluorescence quantitative PCR to detect the tight junction protein Occludin m in mouse jejunum. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum IL-4, IFN-gamma, IL-4/IFN-gamma and sIgA in mouse intestinal mucosa; fluorescence quantitative PCR was used to detect the contents of IL-17, TGF-beta 1, TGF-beta 1/IL-17 mRNA in mouse jejunum. Among the prescriptions, 57 258 were collected, 115 were single, and the prescriptions were tested. Through frequency analysis, it was concluded that antidotes were the main types of drugs, accounting for 45.74%; 48 drugs were used more frequently than or equal to two times, accounting for 41.74%; medicinal properties were mainly cold, accounting for 40.31% and 20.54% respectively; bitterness was the main flavor. The main types of food poisoning were mistaken poisons and food poisoning, accounting for 35.27% and 31.40%; the main treatment areas were digestive system, accounting for 54.64%. The main symptoms were diarrhea and vomiting, accounting for 18.06% respectively. 2. Evaluation index of ovalbumin allergic mice model 2. 1 Allergic symptoms after the first OVA stimulation, the "Yajieshaba" was low, the middle and high dose group of mice allergic symptoms were lower than the model group, but the difference was not unified. The scores of allergic symptoms in the middle and high dose groups were significantly lower than those in the model group (P 0.01). 2.2 After the first OVA stimulation of diarrhea symptoms, the scores of diarrhea in the middle and high dose groups were lower than those in the model group, but only in the middle dose group. There was a significant difference between the two groups (P 0.05). After the second OVA stimulation, the diarrhea fraction of the drug intervention group was significantly lower than that of the model group (P 0.01). 2.3 The serum OVA-IgE level of the drug intervention group was significantly lower than that of the model group (P 0.05). 3 The intestinal flora structure of the drug intervention group was significantly lower than that of the model group (P 0.05). The diversity and richness of Alpha microflora in feces of mice were similar to those of the model group (P 0.05), but the high dosage of Yajieshabao increased both of them. But only the middle dose group had statistical significance (P 0.05). 3.2 mice intestinal microecological composition and distribution of abundance in the "gate" level, compared with the model group, the drug intervention group mice sclerenchyma bacterial proportion showed a decreasing trend, the high dose group was obvious, the difference was statistically significant (P 0.05); and the proportion of Bacteroides bacteria showed an increasing trend, with high dose. There was significant difference between the two groups (P 0.05). Compared with the model group, the number of Lactobacillus bacteria decreased, but the difference was not statistically significant (P 0.05), while the number of Barnesiella bacteria increased, with significant difference in high dose (P 0.05). Compared with the model group, the intestinal mucosal permeability of the drug intervention group was significantly higher than that of the model group, and the expression of Occludin mRNA in the intestinal epithelium of the drug intervention group was significantly higher than that of the model group (P 0.05). There was no significant difference in the expression of in3 mRNA between the two groups (P 0.05). 5 Compared with the model group, the immunological results of intestinal mucosa were lower. The serum IL-4 concentration of the middle dose group was higher, but there was no significant difference (P 0.05). The serum IL-4 concentration of the high dose group was significantly lower than that of the model group (P 0.05). Compared with the model group, the serum IFN-gamma concentration of the drug intervention group was significantly higher, the difference was statistically significant (P 0.01). The drug intervention group had a tendency to lower the serum IL-4/IFN-gamma ratio, but only the high dose ratio was significantly lower (P 0.05). Compared with the model group, the expression of IL-17 mRNA and TGF-beta 1 mRNA in the drug intervention group were significantly lower. There was no significant difference in the expression of TGF-1/IL-17 and sIgA levels (P 0.05). Conclusion 1 The antidote drugs were the main prescriptions for "food poisoning"; the main medicinal properties were cooling, and the main flavor was bitterness; the main compatibility was compound prescriptions, followed the principle of "four towers" and "cold and heat" were balanced. "Yajieshaba" is one of the representative prescriptions of "food poisoning". Intestinal tract is the angle and way of study. Diarrhea is one of the main symptoms of "food poisoning". 3 "Yajieshaba" alleviates the symptoms of ovalbumin-allergic mice by reducing the allergic symptoms, diarrhea, serum OVA-IgE levels. Over-elevating Shannon index, reducing Simpson index, increasing colony diversity and regulating the imbalance of intestinal flora. 5 At the gate level of intestinal microecology, "Yajiesha Bag" can reduce the proportion of sclerenchyma bacteria in mice, increase the proportion of Bacteroides bacteria, restore the imbalance of intestinal flora, and the high dose of "Yajiesha Bat" has a significant effect in the intestine. At the genus level of Tao micro-ecology, Yajieshaba could reduce the proportion of Lactobacillus, increase the proportion of Barnesiella, restore the unbalanced intestinal flora, and the effect of high dose Yajieshaba was significant. 7 Yajieshaba could restore the difference of intestinal microbial community structure in mice. 8 Yajieshaba could increase the Occludin of mice by increasing the proportion of Barnesiella. The content of mRNA, the integrity of intestinal mucosa epithelium and the permeability of intestinal mucosa were protected, but the content of Claudin 3 mRNA was not affected. 9 "Yajieshabao" could regulate the immune imbalance caused by Th2 dominance of immune cells and restore the Th1/Th2 balance by lowering serum IL-4 concentration, increasing IFN-gamma concentration and decreasing the ratio of IL-4 to IFN-gamma in mice. "No effect on the expression of IL-17 mRNA, TGF-beta 1 mRNA, TGF-beta 1/IL-17 ratio and sIgA level was observed. 11" Yajiesha "has a bright future in the treatment of food allergy, especially in high dosage.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R29
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1 李瓊超;基于食物過敏的傣藥“雅解沙把”解“食物毒”作用機(jī)制研究[D];北京中醫(yī)藥大學(xué);2017年
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