翁連解毒湯對(duì)潰瘍性結(jié)腸炎大鼠IL-13、TLR4表達(dá)的影響
發(fā)布時(shí)間：2018-07-28 11:12
【摘要】：目的:潰瘍性結(jié)腸炎(UC)是一種病因尚不明確的直腸和結(jié)腸慢性非特異性炎癥性疾病。病情輕重不一,反復(fù)發(fā)作,且病程較長。本實(shí)驗(yàn)通過觀察翁連解毒湯對(duì)UC模型大鼠一般情況、疾病活動(dòng)指數(shù)(DAI)評(píng)分、結(jié)腸組織病理學(xué)形態(tài)、白細(xì)胞介素-13(IL-13)及Toll樣受體4(TLR4)表達(dá)的影響,探討翁連解毒湯治療潰瘍性結(jié)腸炎的作用機(jī)理,并為臨床應(yīng)用提供實(shí)驗(yàn)依據(jù)。方法:60只Wistar雄性健康清潔級(jí)大鼠(體重220g-250g)適應(yīng)性喂養(yǎng)7天后,隨機(jī)分為空白對(duì)照組(CK組)、模型組(MG組)、美沙拉嗪組(MS組)、中藥高劑量組(HD組)、中劑量組(MD組)及低劑量組(LD組)6組,每組10只,予常規(guī)飼養(yǎng)。除CK組外,其余各組大鼠均采用2,4,6-三硝基苯磺酸(TNBS)/乙醇聯(lián)合造模法設(shè)計(jì)UC大鼠模型。造模成功后第4天開始,CK組不做特殊處理,MG組予4ml/kg生理鹽水灌胃,MS組予美沙拉嗪混懸液灌胃,中藥各組大鼠分別予相應(yīng)劑量的藥物灌胃,連續(xù)藥物干預(yù)2周后觀察治療期間大鼠精神狀態(tài)、食量、體重以及糞便性狀等一般情況的變化,并進(jìn)行DAI評(píng)分。治療結(jié)束后,各組大鼠禁食不禁水24小時(shí),利多卡因麻醉,股動(dòng)脈取血,酶聯(lián)免疫吸附法(ELISA)檢測血清IL-13含量,免疫組化法檢測腸粘膜組織中TLR4的表達(dá)情況。結(jié)果:1一般情況觀察整個(gè)治療期間CK組大鼠精神狀態(tài)良好,喜覓食,體毛光澤整潔,動(dòng)作敏捷,體重增加,糞便為正常的黑色顆粒狀。其余各組大鼠在造模成功后均出現(xiàn)不同程度的稀便或粘液膿血便,且肛周污穢,扎堆嗜蜷臥,不喜活動(dòng),精神差,被毛凌亂無光澤,進(jìn)食量減少。藥物干預(yù)后除MG組大鼠外,HD組、MD組、LD組、MS組四組大鼠精神狀態(tài)、食量、體重等一般情況逐漸改善,稀便及黏液膿血便較前減少。其中以hd組大鼠癥狀改善最明顯,ms組與md組大鼠相比,好轉(zhuǎn)情況無明顯差別,ld組大鼠情況不及以上三組。而mg組大鼠隨著實(shí)驗(yàn)進(jìn)度狀態(tài)每況愈下,稀便或黏液膿血便加重,體重均有不同程度的減輕,精神萎靡,嗜蜷臥,被毛暗淡無光澤,不喜食。2dai評(píng)分結(jié)果hd組、md組、ld組、ms組均低于mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);hd組相較于md組、ld組及ms組三組均低,差異有統(tǒng)計(jì)學(xué)意義(p0.05);md組與ms組均低于ld組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);md組與ms組比較,差異無統(tǒng)計(jì)學(xué)意義(p0.05)。3結(jié)腸組織病理學(xué)觀察ck組大鼠組織表面上皮完整,隱窩長且平直,未見分支、扭曲,杯狀細(xì)胞數(shù)量多,固有膜內(nèi)偶見炎細(xì)胞,黏膜肌層未見增厚,黏膜下層未見血管擴(kuò)張充血和水腫;mg組可見潰瘍表面被覆炎性滲出物及壞死組織,固有膜內(nèi)大量炎細(xì)胞彌漫浸潤;hd組大鼠組織表面上皮完整,隱窩長且平直,偶見分支,杯狀細(xì)胞數(shù)量較多,固有膜內(nèi)可見少量炎細(xì)胞;md組、ms組差異不明顯,組織表面上皮不規(guī)則,隱窩分支少,杯狀細(xì)胞數(shù)量較多,固有膜內(nèi)可見較少炎細(xì)胞;ld組表面上皮不規(guī)則,隱窩呈分支狀并且扭曲,杯狀細(xì)胞數(shù)量明顯減少,隱窩基底部與黏膜肌層距離增加,其間可見大量炎細(xì)胞片狀浸潤,黏膜肌層增厚。4指標(biāo)檢測il-13的表達(dá):ck組il-13表達(dá)均高于hd組、md組、ld組、ms組以及mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);hd組高于md組、ld組、ms組及mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);md組、ms組高于ld組、mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);ld組高于mg組,差異有統(tǒng)計(jì)學(xué)意義(p0.05);md組與ms組相比,無統(tǒng)計(jì)學(xué)意義(p0.05)。tlr4的表達(dá):ck組tlr4表達(dá)低于hd組、md組、ld組、ms組以及mg組,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);hd組低于md組、ld組、ms組及mg組,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);md組、ms組低于ld組、mg組,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);ld組低于mg組,差異具有統(tǒng)計(jì)學(xué)意義(p0.05);md組與ms組比較無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:翁連解毒湯能夠顯著改善潰瘍性結(jié)腸炎大鼠的一般情況和腸黏膜組織的損傷情況,中藥高劑量組效果優(yōu)于其它各治療組,中劑量組與美沙拉嗪組療效相當(dāng),低劑量組療效次之。其作用機(jī)制可能是通過降低腸黏膜組織中TLR4的表達(dá)、上調(diào)IL-13的含量來實(shí)現(xiàn)的,通過影響某種信號(hào)轉(zhuǎn)導(dǎo)通路,增加抑炎因子的釋放,促使促炎因子和抑炎因子趨于動(dòng)態(tài)平衡,從而阻斷細(xì)胞損害過程,刺激局部組織修復(fù)再生,促進(jìn)潰瘍的愈合。
[Abstract]:Objective: ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the rectum and colon which is still unknown. The severity of the disease is different, repeated episodes, and the course of the disease is longer. This experiment was conducted by observing the general condition of the UC model rats, the disease activity index (DAI), the pathological morphology of the colon, and the interleukin -13. IL-13) and the effect of Toll like receptor 4 (TLR4) expression to explore the mechanism of Weng Lian Jiedu Decoction in the treatment of ulcerative colitis and provide experimental basis for clinical application. Methods: 60 Wistar male healthy clean rats (body weight 220g-250g) were fed for 7 days after adaptive feeding, and were randomly divided into blank control group (CK group), model group (MG group), mesalazine group (MS). Group (group HD), medium dose group (group HD), middle dose group (group MD) and low dose group (group LD), 10 rats in each group were given routine feeding. Except for group CK, all the other rats were designed with 2,4,6- three nitrobenzene sulfonic acid (TNBS) / ethanol combined model method to design UC rat model. After building the work, the group CK did not do special treatment, MG group was given 4ml/kg saline irrigation. The stomach and MS group were given the mesalazine suspension for gastric perfusion, and the rats in each group were given the corresponding dose of medicine. After 2 weeks of continuous drug intervention, the general situation of mental state, food intake, weight and fecal traits were observed and the DAI scores were observed. After the treatment of the knot, the rats in each group were fasting for 24 hours, lidocaine anesthesia. The content of serum IL-13 was detected by the femoral artery and enzyme linked immunosorbent assay (ELISA), and the expression of TLR4 in the intestinal mucosa was detected by immunohistochemical method. Results: 1 the general situation observed that the mental state of the rats in the CK group was good during the whole treatment period, looking for food, the shiny of the body hair was neat, the movement was agile, the weight was increased, and the feces as normal black granules. After the success of the model, the rats in all groups had different degrees of dilute stool or mucous pus and stool, and the perianal filth was filth, and had a bad mood, poor spirit, lustrous, and less eating. After the intervention of the MG group, the mental state of the four groups of rats in group HD, MD, LD and MS gradually improved, and the general condition of the diet, weight and weight gradually improved. The dilute stool and mucus pus and blood stool decreased more than that in the HD group. There was no obvious difference between the group MS and the MD group. In group LD, the condition of the rats was less than the above three groups. And the rats in group mg were worse with the progress of the experiment, and the weight of the dilute stool or mucus pus and blood was added, and the body weight was reduced in varying degrees, and the spirit was dispirited. In group MD, group MD, group LD, MS group were lower than group mg, and the difference was statistically significant (P0.05); HD group was lower than group MD, LD group and MS group were lower in HD group than in group MD (P0.05), and the difference was statistically significant (.2dai). The study significance (P0.05).3 colon histopathology observed that the tissue surface epithelium of group CK rats was complete, the recess long and straight, no branches, distortion, the number of goblet cells, innate inflammatory cells in the lamina propria, no thickening of the mucous membrane, and no vasodilator congestion and edema in the submucosa; in group mg, the surface of the ulcer was covered with inflammatory exudation and necrosis. Tissue, a large number of inflammatory cells infiltrated in the innate membrane; in group HD, the surface epithelium of the rats was complete, the crypts were long and straight, the number of goblet cells was more, the number of goblet cells was more, and a small amount of inflammatory cells were seen in the propria. In group MD, the differences in the MS group were not obvious, the epithelial epithelium was irregular, the crypts were small, the number of goblet cells were more, and the propri was less inflammatory. The surface epithelium of the LD group was irregular, the crypts were branched and twisted, the number of goblet cells decreased obviously, the distance between the basement and mucous layer of the recess increased, and a large number of inflammatory cells were infiltrated, and the.4 index of the muscularis layer thickened to detect the expression of IL-13. The IL-13 table in group CK was higher than that of the HD group, MD, LD, MS and Mg groups were different. Group HD was higher than group MD, group LD, MS group and mg group, the difference was statistically significant (P0.05); MD group, MS group was higher than LD group and mg group, the difference was statistically significant (P0.05). Group s and mg group, the difference was statistically significant (P0.05), and group HD was lower than group MD, LD group, MS group and mg group, and the difference was statistically significant (P0.05); MD group and MS group were lower than LD group, and the difference had statistical significance. Jiedu Decoction can significantly improve the general condition of ulcerative colitis and the damage of intestinal mucosa. The effect of high dose group of Chinese medicine is better than that of other treatment groups. The effect of medium dose group is equal to that of mesalazine group, and the effect of low dose group is second. The mechanism of its action may be to reduce the expression of TLR4 in intestinal mucosa and up regulation of IL-13. The content is achieved by affecting a signal transduction pathway, increasing the release of anti inflammatory factors and promoting the dynamic balance of proinflammatory and anti inflammatory factors, thus blocking the process of cell damage, stimulating the local tissue to repair and regenerating and promoting the healing of the ulcer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5
本文編號(hào)：2149942
[Abstract]:Objective: ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the rectum and colon which is still unknown. The severity of the disease is different, repeated episodes, and the course of the disease is longer. This experiment was conducted by observing the general condition of the UC model rats, the disease activity index (DAI), the pathological morphology of the colon, and the interleukin -13. IL-13) and the effect of Toll like receptor 4 (TLR4) expression to explore the mechanism of Weng Lian Jiedu Decoction in the treatment of ulcerative colitis and provide experimental basis for clinical application. Methods: 60 Wistar male healthy clean rats (body weight 220g-250g) were fed for 7 days after adaptive feeding, and were randomly divided into blank control group (CK group), model group (MG group), mesalazine group (MS). Group (group HD), medium dose group (group HD), middle dose group (group MD) and low dose group (group LD), 10 rats in each group were given routine feeding. Except for group CK, all the other rats were designed with 2,4,6- three nitrobenzene sulfonic acid (TNBS) / ethanol combined model method to design UC rat model. After building the work, the group CK did not do special treatment, MG group was given 4ml/kg saline irrigation. The stomach and MS group were given the mesalazine suspension for gastric perfusion, and the rats in each group were given the corresponding dose of medicine. After 2 weeks of continuous drug intervention, the general situation of mental state, food intake, weight and fecal traits were observed and the DAI scores were observed. After the treatment of the knot, the rats in each group were fasting for 24 hours, lidocaine anesthesia. The content of serum IL-13 was detected by the femoral artery and enzyme linked immunosorbent assay (ELISA), and the expression of TLR4 in the intestinal mucosa was detected by immunohistochemical method. Results: 1 the general situation observed that the mental state of the rats in the CK group was good during the whole treatment period, looking for food, the shiny of the body hair was neat, the movement was agile, the weight was increased, and the feces as normal black granules. After the success of the model, the rats in all groups had different degrees of dilute stool or mucous pus and stool, and the perianal filth was filth, and had a bad mood, poor spirit, lustrous, and less eating. After the intervention of the MG group, the mental state of the four groups of rats in group HD, MD, LD and MS gradually improved, and the general condition of the diet, weight and weight gradually improved. The dilute stool and mucus pus and blood stool decreased more than that in the HD group. There was no obvious difference between the group MS and the MD group. In group LD, the condition of the rats was less than the above three groups. And the rats in group mg were worse with the progress of the experiment, and the weight of the dilute stool or mucus pus and blood was added, and the body weight was reduced in varying degrees, and the spirit was dispirited. In group MD, group MD, group LD, MS group were lower than group mg, and the difference was statistically significant (P0.05); HD group was lower than group MD, LD group and MS group were lower in HD group than in group MD (P0.05), and the difference was statistically significant (.2dai). The study significance (P0.05).3 colon histopathology observed that the tissue surface epithelium of group CK rats was complete, the recess long and straight, no branches, distortion, the number of goblet cells, innate inflammatory cells in the lamina propria, no thickening of the mucous membrane, and no vasodilator congestion and edema in the submucosa; in group mg, the surface of the ulcer was covered with inflammatory exudation and necrosis. Tissue, a large number of inflammatory cells infiltrated in the innate membrane; in group HD, the surface epithelium of the rats was complete, the crypts were long and straight, the number of goblet cells was more, the number of goblet cells was more, and a small amount of inflammatory cells were seen in the propria. In group MD, the differences in the MS group were not obvious, the epithelial epithelium was irregular, the crypts were small, the number of goblet cells were more, and the propri was less inflammatory. The surface epithelium of the LD group was irregular, the crypts were branched and twisted, the number of goblet cells decreased obviously, the distance between the basement and mucous layer of the recess increased, and a large number of inflammatory cells were infiltrated, and the.4 index of the muscularis layer thickened to detect the expression of IL-13. The IL-13 table in group CK was higher than that of the HD group, MD, LD, MS and Mg groups were different. Group HD was higher than group MD, group LD, MS group and mg group, the difference was statistically significant (P0.05); MD group, MS group was higher than LD group and mg group, the difference was statistically significant (P0.05). Group s and mg group, the difference was statistically significant (P0.05), and group HD was lower than group MD, LD group, MS group and mg group, and the difference was statistically significant (P0.05); MD group and MS group were lower than LD group, and the difference had statistical significance. Jiedu Decoction can significantly improve the general condition of ulcerative colitis and the damage of intestinal mucosa. The effect of high dose group of Chinese medicine is better than that of other treatment groups. The effect of medium dose group is equal to that of mesalazine group, and the effect of low dose group is second. The mechanism of its action may be to reduce the expression of TLR4 in intestinal mucosa and up regulation of IL-13. The content is achieved by affecting a signal transduction pathway, increasing the release of anti inflammatory factors and promoting the dynamic balance of proinflammatory and anti inflammatory factors, thus blocking the process of cell damage, stimulating the local tissue to repair and regenerating and promoting the healing of the ulcer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 孟曉燕;查安生;;潰瘍性結(jié)腸炎緩解期的中醫(yī)復(fù)發(fā)機(jī)制及治療進(jìn)展[J];中醫(yī)藥臨床雜志;2016年11期
2 徐慧艷;李賀薇;謝晶日;;謝晶日經(jīng)方化裁治療潰瘍性結(jié)腸炎的經(jīng)驗(yàn)總結(jié)[J];遼寧中醫(yī)雜志;2016年10期
3 王瑞;劉冬梅;;劉冬梅教授治療潰瘍性結(jié)腸炎的臨床經(jīng)驗(yàn)[J];光明中醫(yī);2016年17期
4 譚朝暉;劉榮火;鄒立華;曹平;胡紅松;;白頭翁湯對(duì)潰瘍性結(jié)腸炎黏膜愈合的影響及部分機(jī)制研究[J];中國中醫(yī)藥信息雜志;2016年07期
5 趙益;賴小東;葉爭榮;劉紅寧;徐國良;;葛根芩連湯對(duì)潰瘍性結(jié)腸炎模型大鼠抗氧化及抗炎的作用機(jī)制[J];中華中醫(yī)藥雜志;2016年05期
6 林燕萍;葉柏;;葉柏教授從肺脾論治潰瘍性結(jié)腸炎(大腸濕熱證)的經(jīng)驗(yàn)[J];中國中醫(yī)急癥;2016年04期
7 陸紅娟;嚴(yán)銀波;;潰瘍性結(jié)腸炎患者飲食日記本的設(shè)計(jì)與應(yīng)用[J];世界最新醫(yī)學(xué)信息文摘;2016年30期
8 黃海蕾;顧勤;;清熱化濕法對(duì)潰瘍性結(jié)腸炎免疫功能影響的研究[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2016年06期
9 周敏紅;葉柏;;葉柏教授從肺論治潰瘍性結(jié)腸炎緩解期臨床經(jīng)驗(yàn)淺析[J];四川中醫(yī);2016年02期
10 専登輝;柳越冬;;王長洪教授治療潰瘍性結(jié)腸炎的經(jīng)驗(yàn)總結(jié)[J];內(nèi)蒙古中醫(yī)藥;2016年02期
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