發(fā)布時(shí)間：2018-06-20 10:09

  本文選題：NAFLD + AQP7��； 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:觀察祛痰活血顆粒治療NAFLD模型大鼠后脂肪組織AQP7、P38MAPK的表達(dá)變化,探討其治療NAFLD的作用機(jī)制。方法:選擇40只體重在180~220g清潔級(jí)雄性SD大鼠,普通飼料適應(yīng)性飼養(yǎng)1周后,按隨機(jī)數(shù)字表法分成正常組(6只)、模型組(34只);正常組給予普通飼料飼喂,模型組采用高脂飲食誘導(dǎo)的方法復(fù)制NAFLD大鼠模型,于第10周開(kāi)始,每隔2周隨機(jī)抽取1~2只大鼠處死,取肝臟做病理染色,觀察其病理變化,確認(rèn)造模成功后,將剩余模型組再隨機(jī)分為模型對(duì)照組6只,中藥高劑量組(6只)、中劑量組(6只)、低劑量組(6只),抑制劑組(6只),各中藥組灌喂祛痰活血顆粒,抑制劑組腹腔注射P38MAPK抑制劑(SB203580)干預(yù),連續(xù)干預(yù)4周后處死大鼠,光鏡下觀察肝臟HE染色及油紅O染色變化,測(cè)定各組大鼠血清TG、TC、AST、ALT,肝臟TG、FFA,肝臟指數(shù)和脂肪組織AQP7及P38MAPK基因及蛋白表達(dá)。結(jié)果:1、病理組織HE及油紅O染色示:與正常組比較,模型組大鼠肝細(xì)胞內(nèi)脂滴數(shù)量多,肝臟脂肪變性明顯,差異有統(tǒng)計(jì)學(xué)意義(P0.05);與模型組比較,中藥組與抑制劑組大鼠肝細(xì)胞內(nèi)脂滴數(shù)量減少,肝臟脂肪變性程度明顯減輕(P0.05);2、血清生化指標(biāo)示:與正常組比較,模型組大鼠的血清TG、TC、AST、ALT明顯升高;與模型組比較,各中藥組及抑制劑組大鼠的血清TG、TC、AST、ALT明顯降低(P0.05);3、肝臟tg、ffa及肝臟指數(shù)示:與正常組比較,模型組大鼠的肝臟tg、ffa和肝臟指數(shù)明顯升高;與模型組比較,中藥組及抑制劑組大鼠的肝臟tg、ffa和肝臟指數(shù)明顯降低(p0.05);4、realtime-pcr檢測(cè)結(jié)果示:與正常組比較,模型組大鼠脂肪組織中aqp7mrna表達(dá)降低,p38mapkmrna表達(dá)升高(p0.05);與模型組比較,各中藥組和抑制劑組大鼠脂肪組織中aqp7mrna表達(dá)明顯升高,以中藥高劑量組效果最好;p38mapkmrna表達(dá)明顯降低,以抑制劑組效果最明顯,中藥高劑量組效果次之(p0.05);中藥低、中劑量組大鼠間的aqp7和p38mapkmrna表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);5、蛋白檢測(cè)結(jié)果示:與正常組比較,模型組大鼠脂肪組織中aqp7蛋白表達(dá)明顯降低,p-p38mapk蛋白表達(dá)明顯升高(p0.05);與模型組比較,各中藥組和抑制劑組大鼠脂肪組織中aqp7蛋白表達(dá)明顯升高,以中藥高劑量組效果最好;p-p38mapk蛋白表達(dá)明顯降低,以抑制劑組效果最明顯,中藥高劑量組效果次之(p0.05);中藥低、中劑量組大鼠間aqp7和p-p38mapk蛋白表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05);各組大鼠脂肪組織總p38mapk蛋白無(wú)明顯差異(p0.05)。結(jié)論:1、祛痰活血顆�？筛纳苙afld的病理結(jié)構(gòu),減輕nafld大鼠肝臟脂肪變性程度及肝臟炎癥;2、祛痰活血顆�？山档蚽afld大鼠肝臟指數(shù)、血清tg、tc、ast、alt及肝臟tg、ffa;3、祛痰活血顆�？赡芡ㄟ^(guò)抑制脂肪組織中p38mapk活化、上調(diào)aqp7表達(dá),增加甘油入血代謝,減少進(jìn)入肝臟的甘油及ffa,從而減少肝臟脂肪蓄積,減輕肝脂脂肪變性程度;4、脂肪組織中p38mapk通路可能參與抑制AQP7的表達(dá),起到調(diào)控甘油及脂肪代謝,從而間接改善NAFLD。
[Abstract]:Objective: to observe the changes of AQP7 and P38 MAPK expression in adipose tissue of NAFLD rats treated with Quphan Huoxue granule and to explore the mechanism of its therapeutic effect on NAFLD. Methods: forty male SD rats weighing 180 ~ 220g were selected and fed with normal diet for one week, then were randomly divided into normal group (n = 6), model group (n = 34) and normal group (n = 34). In the model group, NAFLD rat model was induced by high-fat diet. From the 10th week on, 2 rats were randomly selected every 2 weeks to be killed. The liver was taken for pathological staining, the pathological changes were observed, and the model was established successfully. The remaining model group was randomly divided into two groups: control group (n = 6), high dose group (n = 6), middle dose group (n = 6), low dose group (n = 6) and inhibitor group (n = 6). The rats in the inhibitor group were treated with P38 MAPK inhibitor SB203580 intraperitoneally. The rats were killed after 4 weeks of continuous intervention. The liver HE staining and oil red O staining were observed under light microscope. The levels of serum TGG, liver TGfFA, AQP7 and P38 MAPK gene and protein expression in adipose tissue were measured. Results: the pathological tissues were stained with HE and oil red O: compared with the normal group, the rats in the model group had more lipid droplets and steatosis in the liver, the difference was statistically significant (P 0.05), and compared with the model group, there was no significant difference between the model group and the model group. The number of lipid droplets in liver cells in the Chinese medicine group and the inhibitor group were decreased, and the degree of steatosis in the liver was significantly reduced (P 0.05). The serum biochemical indexes showed that compared with the normal group, the serum TGN TCASTN alt of the model group was significantly higher than that of the model group, and that of the model group was significantly higher than that of the model group. The serum levels of TGG, TCC, AST and liver index of rats in the traditional Chinese medicine group and the inhibitor group were significantly lower than those in the control group, and the liver tgffa and liver index in the model group were significantly higher than those in the model group, and in comparison with the model group, the liver index of the model group was significantly higher than that of the control group, and that of the model group was significantly higher than that of the control group. Compared with the normal group, the expression of aqp7mrna in the adipose tissue of the model group decreased significantly, and the expression of p38 mapkmrna increased in the model group, and compared with the model group, the liver index of the rats in the traditional Chinese medicine group and the inhibitor group was significantly decreased, and that in the model group was significantly higher than that in the model group, the results showed that: compared with the model group, the expression of aqp7mrna in the adipose tissue of the model group was significantly lower than that in the control group. The expression of aqp7mrna in adipose tissue of rats in each Chinese medicine group and inhibitor group was significantly increased, and the expression of p38 mapkrna was the best in the high dose group, especially in the inhibitor group, followed by p0.05 in the high dose group, and low in the Chinese medicine group, and the expression of p38mapkmrna in the high dose group was lower than that in the control group. There was no significant difference in the expression of aqp7 and p38mapkmrna between the middle dose group and the middle dose group. The results of protein detection showed that the expression of aqp7 protein in adipose tissue of the model group was significantly lower than that in the normal group, and the expression of p-p38 mapk protein was significantly increased in the model group, while that in the model group was significantly higher than that in the model group. The expression of aqp7 protein in adipose tissue of rats in each Chinese medicine group and inhibitor group was significantly increased, and the expression of p-p38 mapk protein was the best in high dose group, especially in inhibitor group, followed by p0.05 in high dose group and low in Chinese medicine group. There was no significant difference in the expression of aqp7 and p-p38mapk protein between the middle dose group and the adipose tissue of the rats in each group (p 0.05), but there was no significant difference in the total p38mapk protein in the adipose tissue of the rats in each group (P 0.05). Conclusion: W1, Quphan Huoxue granule can improve the pathological structure of nafld, reduce the degree of hepatic steatosis and liver inflammation in nafld rats. Quphlegm Huoxue granule can reduce the liver index of nafld rats. Serum TGP tcastan and liver tgctctcastastan and liver TGP 3. Quphlegm Huoxue granule may reduce hepatic fat accumulation by inhibiting p38mapk activation in adipose tissue, upregulating aqp7 expression, increasing glycerol metabolism, reducing glycerol and FFA entering the liver, and reducing liver fat accumulation. In adipose tissue, p38mapk pathway may be involved in inhibiting AQP7 expression, regulating glycerol and fat metabolism, and thus indirectly improving NAFLD.
【學(xué)位授予單位】：西南醫(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;R-332

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