本文選題：巴豆醛 + 雄性大鼠��； 參考：《濟(jì)南大學(xué)》2016年碩士論文

【摘要】：巴豆醛(Crotonaldehyde),其化學(xué)結(jié)構(gòu)式為CH3CH=CHCHO,其有順式和反式兩種雙鍵異構(gòu)體。通常為無(wú)色或略帶黃色的液體,可以燃燒,具有催淚性,暴露于空氣中或遇到光照時(shí)逐漸變?yōu)榈S色液體,隨即被氧化為巴豆酸。巴豆醛可經(jīng)口、鼻及皮膚等途徑侵入機(jī)體,具有明顯的刺激作用和催淚作用。然而,國(guó)內(nèi)外對(duì)巴豆醛的動(dòng)物毒理學(xué)實(shí)驗(yàn)研究資料極少,因此本實(shí)驗(yàn)以雄性大鼠為對(duì)象進(jìn)行毒研究,旨在全面探討巴豆醛的毒理學(xué)損傷特性�！狙芯磕康摹砍醪教接懓投谷⿲�(duì)雄性大鼠的毒性損傷作用,為近一步研究巴豆醛對(duì)作業(yè)人群的生物監(jiān)測(cè)和健康監(jiān)護(hù)方案提供重要依據(jù)和線(xiàn)索,并彌補(bǔ)國(guó)內(nèi)、外相關(guān)資料的缺失�！狙芯糠椒ā�1.巴豆醛對(duì)大鼠的急性經(jīng)口毒性研究選擇SPF級(jí)健康Wistar大鼠40只,體重在180~220克之間按照雌雄各分為4組,每組5只,動(dòng)物禁食12小時(shí)后灌胃給藥,根據(jù)預(yù)試驗(yàn)結(jié)果設(shè)計(jì)染毒劑量為215、100、46.4、21.5mg/kg。動(dòng)物染毒后連續(xù)觀(guān)察14天,其間觀(guān)察和記錄動(dòng)物中毒癥狀及死亡情況,最后根據(jù)每組動(dòng)物數(shù)、組距和每組動(dòng)物死亡數(shù),即可從霍恩氏表中查得半數(shù)致死量(LD50)及其95%可信限。2.巴豆醛對(duì)大鼠的蓄積毒性研究本次實(shí)驗(yàn)選取40只健康Wistar大鼠,隨機(jī)分為2組,每組20只,雌雄各半,采用固定劑量法染毒,實(shí)驗(yàn)組大鼠每天經(jīng)口染毒1/5LD50劑量的巴豆醛,連續(xù)灌胃染毒28d,對(duì)照組大鼠給予同劑量的溶劑。實(shí)驗(yàn)期內(nèi)大鼠累計(jì)死亡數(shù)達(dá)50%,終止實(shí)驗(yàn)。按照公式計(jì)算蓄積系數(shù)(K),以評(píng)價(jià)化合物對(duì)機(jī)體蓄積性毒性的大小。3.巴豆醛對(duì)雄性大鼠的亞慢性毒性研究選取SPF級(jí)健康Wistar雄性大鼠40只,體重在190~200克之間,待大鼠適應(yīng)性飼養(yǎng)1周后,隨機(jī)分為4組,每組10只,分為高、中、低3個(gè)劑量組(染毒劑量分別為8.44mg/kg、4.22mg/kg、2.11mg/kg)和1個(gè)對(duì)照組,對(duì)照組給予蒸餾水處理。經(jīng)口灌胃,每天1次,連續(xù)染毒28d。最后一次染毒結(jié)束24h后,采用頸椎脫臼法處死大鼠,迅速摘取大鼠主要臟器,稱(chēng)重并計(jì)算臟器系數(shù)。摘眼球取血法采取大鼠外周血,全自動(dòng)血生化分析儀測(cè)血清生化指標(biāo);酶聯(lián)免疫吸附法(elisa法)測(cè)定氧化損傷指標(biāo);常規(guī)he染色觀(guān)察肝組織病理學(xué)改變;流式細(xì)胞術(shù)(fcm)進(jìn)行淋巴細(xì)胞亞群分析;酶聯(lián)免疫吸附法(elisa)檢測(cè)大鼠外周血及組織中細(xì)胞因子表達(dá)水平�！狙芯拷Y(jié)果】1.巴豆醛對(duì)大鼠的急性經(jīng)口毒性及蓄積毒性研究查霍恩氏表可得,巴豆醛對(duì)雌雄wistar大鼠的急性經(jīng)口ld50如下:雌性大鼠為147mg/kg,95%可信限為95.1-227mg/kg;雄性大鼠為42.2mg/kg,95%可信限為25.3-70.2mg/kg。按照化學(xué)品毒理學(xué)分級(jí)標(biāo)準(zhǔn),巴豆醛為高毒化學(xué)品。采用固定計(jì)量法,根據(jù)公式求得蓄積系數(shù)k5,認(rèn)為巴豆醛有輕度蓄積毒性。2.巴豆醛對(duì)雄性大鼠的亞慢性毒性研究與對(duì)照組相比,高劑量組大鼠體重增重減少,肝臟臟器系數(shù)明顯增高,且隨著染毒劑量的增加,肝臟系數(shù)有增高的趨勢(shì);血清中谷丙轉(zhuǎn)氨酶(alt)和谷草轉(zhuǎn)氨酶(ast)水平明顯增加,高劑量組和中劑量組的mda含量升高,sod含量降低,高劑量組的gsh-px含量降低,差異均有統(tǒng)計(jì)學(xué)意義(p0.05);與對(duì)照組相比,心臟系數(shù)、脾臟系數(shù)、腎臟系數(shù)及血清中總膽紅素(tbil)、尿素(bun)、尿酸(ua)、肌酐(cre)、葡萄糖(glu)、甘油三酯(tg)、總膽固醇(chol)水平無(wú)明顯變化,差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);病理組織切片顯示大鼠肝組織有炎性損傷;與對(duì)照組比較,各劑量組大鼠外周血中cd3+cd8+(%)、cd3+cd4+(%)及cd3(%)均無(wú)明顯改變,差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);與對(duì)照組比較,各組大鼠血清中il-4、il-6和tnf-α組間含量差異有統(tǒng)計(jì)學(xué)意義(p0.05),且隨著染毒劑量的增加,各組il-4、il-6和tnf-α的含量呈升高的趨勢(shì),且高劑量組變化最為明顯;與對(duì)照組比較,各組大鼠血清中il-1b及ifn-γ組間變化不明顯,差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);與對(duì)照組比較,各組大鼠肝臟組織中il-4、il-6、ifn-γ和tnf-α組間含量差異有統(tǒng)計(jì)學(xué)意義(p0.05),且隨著染毒劑量的增加,各組l-4、il-6、ifn-γ和tnf-α的含量呈升高的趨勢(shì);與對(duì)照組比較,各組大鼠肝臟組織中il-1b組間變化不明顯,差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);與對(duì)照組比較,各組大鼠肺臟組織中il-1b組間含量差異有統(tǒng)計(jì)學(xué)意義(p0.05),且隨著染毒劑量增加,il-1b含量也增加,高劑量組變化最為顯著;與對(duì)照組比較,各組大鼠肺臟組織中IL-4、IL-6、IFN-γ和TNF-α組間變化不明顯,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);與對(duì)照組比較,各組大鼠腎臟組織中IL-1b、IL-4、IL-6、IFN-γ和TNF-α的表達(dá)水平組間變化不明顯,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。【研究結(jié)論】1.巴豆醛對(duì)雌雄Wistar大鼠的急性經(jīng)口LD50如下:雌性大鼠為147mg/kg,95%可信限為95.1-227mg/kg;雄性大鼠為42.2mg/kg,95%可信限為25.3-70.2mg/kg。按照化學(xué)品毒理學(xué)分級(jí)標(biāo)準(zhǔn),巴豆醛屬于高毒化學(xué)品,且對(duì)雄性大鼠較為敏感。根據(jù)蓄積毒性實(shí)驗(yàn)結(jié)果(K5),可以認(rèn)為巴豆醛對(duì)大鼠有輕度蓄積毒性,為下一步進(jìn)行亞急性毒性研究的染毒劑量選擇提供了參考依據(jù)。2.巴豆醛經(jīng)口染毒導(dǎo)致雄性大鼠體重增重下降,肝臟的臟器系數(shù)明顯增加。3.巴豆醛對(duì)雄性大鼠肝臟組織造成病理?yè)p傷,且損傷程度隨染毒劑量的增加而增高。4.巴豆醛導(dǎo)致雄性大鼠血液中生化指標(biāo)ALT、AST的升高,反應(yīng)了肝臟受損。氧化應(yīng)激指標(biāo)MDA含量升高,SOD含量降低,說(shuō)明機(jī)體受到自由基攻擊。5.巴豆醛染毒導(dǎo)致肝組織勻漿中IL-4、IL-6、IFN-γ和TNF-α水平升高,說(shuō)明巴豆醛對(duì)肝臟組織有炎性損傷。
[Abstract]:Crotonaldehyde, its chemical structural formula is CH3CH=CHCHO, which has two kinds of CIS and trans isomers. Usually colorless or slightly yellow liquid, it can be burned, teary, exposed to air or when exposed to light, gradually changed into yellowish liquid, which is oxidized to bean acid. The way to invade the body has obvious stimulating effect and leardrop effect. However, there are few experimental data on animal toxicology of croton aldehyde at home and abroad. Therefore, this experiment took the male rats as the object to study the toxicological properties of the soybean aldehyde in an all-round way. The effect of toxic damage can provide an important basis and clue to study the biological monitoring and health monitoring program of the operating crowd, and make up for the lack of related data in China. [method] 1. the study of acute oral toxicity of 1. soybean aldehyde to rats, 40 rats of SPF grade healthy Wistar were selected and the weight was between 180~220 grams. The female and male were divided into 4 groups, each group was 5. After fasting for 12 hours, the animals were given the medicine for 12 hours. According to the results of the pre test, the poisoned dose was observed for 14 days. The symptoms and death conditions of the animals were observed and recorded. Finally, the number of animals in each group, the distance from the group and the number of death in each group could be obtained from Hun's family. 40 healthy Wistar rats were randomly divided into 2 groups, 20 rats in each group were randomly divided into 2 groups, 20 in each group and half of male and male in each group. The experimental group was infected with fixed dose method. The experimental group was exposed to 1/ 5LD50 dose of Wistar aldehyde in the experimental group every day. The rats were continuously exposed to 28d and the control group. The rats were given the same dose of solvent. The cumulative death number of rats in the experimental period was 50% and the experiment was terminated. The cumulative coefficient of accumulation (K) was calculated according to the formula to evaluate the size of the cumulative toxicity of the compound to the body.3.. The subchronic toxicity study of the male rats was selected by the SPF grade healthy Wistar male rats. The weight of the male rats was in the 190~200 gram, and the rat was suitable for the rat. After 1 weeks of sexual rearing, they were randomly divided into 4 groups, 10 in each group, which were divided into high, middle and low 3 doses group (8.44mg/kg, 4.22mg/kg, 2.11mg/kg) and 1 control groups. The control group was treated with distilled water. After the oral administration of the stomach, the rats were infected with 28d. for the last time 24h, and the rats were killed by dislocated cervical vertebra and exiexed quickly. The main organs of the rat were weighed and the organ coefficients were weighed. The peripheral blood of rats was taken by taking the eyeball extraction method, the biochemical indexes of the serum were measured by the automatic blood biochemical analyzer; the oxidative damage index was measured by the enzyme linked immunosorbent assay (ELISA method); the pathological changes of liver tissues were observed by the routine HE staining; the lymphocyte subsets were analyzed by flow cytometry (FCM); enzyme linked immunization The expression level of cytokine in the peripheral blood and tissue of rats was detected by ELISA. [results] 1. the acute oral toxicity and accumulation toxicity of croton aldehyde to rats was obtained. The acute oral LD50 of the female and male Wistar rats was as follows: the female rats were 147mg/kg, and the male rats were 95.1-227mg/kg; the male rats were 95.1-227mg/kg. For 42.2mg/kg, the 95% confidence limit is 25.3-70.2mg/kg. according to the classification standard of Chemical Toxicology and the soybean aldehyde is a high toxic chemical. The fixed measurement method is used to obtain the accumulation coefficient K5 according to the formula. It is believed that the subchronic toxicity of the soybean aldehyde with mild cumulative toxic.2. to the male rats is compared with the control group, the weight gain of the high dose group is increased. The coefficient of liver organs increased significantly, and the liver coefficient increased with the increase of dose. The level of ALT and AST in the serum increased significantly, the MDA content in the high dose group and the middle dose group increased, the content of SOD decreased, and the GSH-Px content in the high dose group decreased, the difference was statistically significant (p0.0 5): compared with the control group, the cardiac coefficient, spleen coefficient, kidney coefficient and serum total bilirubin (TBIL), urea (BUN), uric acid (UA), creatinine (CRE), glucose (Glu), triglyceride (TG), total cholesterol (Chol) level had no significant change, and the difference was not statistically significant (P0.05); pathological tissue section showed inflammatory injury in rat liver tissue; and control group. There was no significant change in cd3+cd8+ (%), cd3+cd4+ (%) and CD3 (%) in the peripheral blood of rats in each dose group, and there was no significant difference (P0.05). Compared with the control group, there was a significant difference in the content of IL-4, IL-6 and tnf- alpha in the serum of each group (P0.05), and the content of IL-4, IL-6 and tnf- alpha in each group increased with the increase of the dose. There was no significant change between IL-1B and ifn- gamma groups in the serum of rats in the control group, and there was no significant difference (P0.05). Compared with the control group, the differences in the content of IL-4, IL-6, ifn- gamma and tnf- alpha in the liver tissues of the rats were statistically significant (P0.05), and with the increase of dosage, each group had a significant difference (P0.05). The content of L-4, IL-6, ifn- gamma and tnf- alpha in the group of rats was increased. Compared with the control group, there was no significant difference between the IL-1B groups in the liver tissues of the rats (P0.05). Compared with the control group, the difference in the content of the IL-1B groups in the lung tissues of the rats in each group had a statistical significance (P0.05), and as the dose increased, the IL-1B content was also increased. In the control group, the changes of IL-4, IL-6, IFN- gamma and TNF- a were not significant (P0.05). Compared with the control group, there was no significant difference in the expression of IL-1b, IL-4, IL-6, IFN- gamma and TNF- alpha in the kidney tissues of the rats. The differences were not statistically significant, and the difference was not statistically significant. Significance (P0.05). [Conclusion] [Conclusion] 1. the acute oral LD50 of the female and male Wistar rats is as follows: the female rats are 147mg/kg, the 95% confidence limit is 95.1-227mg/kg, the male rats are 42.2mg/kg, the 95% confidence limit is 25.3-70.2mg/kg. according to the chemical toxicology grading standard, and the soybean aldehyde belongs to the high toxic chemical, and it is more sensitive to the male rats. According to the results of the cumulative toxicity test (K5), it can be considered that the croton aldehyde has a mild cumulative toxicity to rats, which provides a reference basis for the next step of subacute toxicity study, which provides a reference basis for the weight gain of the male rats induced by the oral administration of.2., and the organ coefficient of the liver is significantly increased by the.3. of the male rat liver. The pathological damage was caused by the histopathology, and the damage degree increased with the increase of the dose of.4., which resulted in the increase of ALT and AST in the blood of the male rats and the liver damage. The oxidative stress index MDA content increased and the SOD content decreased, indicating that the body was exposed to the free radical attack of.5., which resulted in the IL-4, IL-6, IFN- in the liver homogenate. Elevated levels of gamma and TNF- alpha indicate that croton aldehyde has inflammatory injury to liver tissue.
【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R114

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