二甲双胍对2型糖尿病合并非酒精性脂肪肝大鼠肝脏功能及炎症反应的影响

发布时间：2018-05-15 12:52

本文选题：型糖尿病 + 二甲双胍　；参考：《山东医药》2017年30期

【摘要】：目的探讨二甲双胍对2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)大鼠肝功能及炎症反应的影响。方法取40只大鼠,随机分为A组(T2DM+NAFLD+二甲双胍组)、B组(T2DM+NAFLD组)、C组(T2DM组)、D组(空白对照组)各10只。A、B组均予以高糖高脂饲料喂养4周制备NAFLD模型,C组予以基础饲料喂养4周,D组仅以基础饲料喂养8周。A、B、C组一次性腹腔注射STZ制备T2DM模型。造模4周后,A组予二甲双胍150 mg/(kg·d)灌胃4周,B、C、D组均予以等量生理盐水灌胃4周。各组干预结束后,麻醉大鼠,腹主动脉穿刺取血,检测血脂(TC、TG、HDL-C、LDL-C)、肝功能(ALT、AST、GGT)及血清TNF-α、IL-6水平。取肝脏组织,计算肝指数。采用HE染色法观察肝脏组织病理学变化。采用免疫组化法及Western blotting法检测肝脏组织TNF-α、IL-6蛋白表达。结果 (1)B、C组TC、TG、LDL-C、GGT、ALT、AST均高于D组,HDL-C低于D组(P均0.05或0.01)。A组TC、TG、LDL-C、GGT、ALT、AST均低于B组,HDL-C高于B组(P均0.05或0.01)。(2)B、C组血清TNF-α、IL-6均高于D组,A组血清TNF-α、IL-6水平均低于B组(P均0.05或0.01)。(3)B、C组肝指数均高于D组,A组肝指数低于B组(P均0.01)。(4)D组肝组织结构完整,肝小叶结构正常。B、C组肝脏组织呈脂肪样变,部分可见小叶内炎性细胞浸润。A组肝脏脂肪变性程度及炎性细胞浸润较B组明显减轻。(5)B、C组肝脏组织中TNF-α、IL-6蛋白表达均高于D组(P均0.01),A组肝脏组织中TNF-α、IL-6蛋白表达均低于B组(P均0.05)。结论二甲双胍可明显改善T2DM合并NAFLD大鼠的肝脏功能,抑制NAFLD的发生发展;其机制可能为通过降低炎性因子的表达、改善慢性炎症状态,从而发挥肝脏保护作用。
[Abstract]:Objective to investigate the effects of metformin on liver function and inflammatory response in type 2 diabetic rats with non alcoholic fatty liver disease (NAF LDD). Methods Forty rats were selected. Group A was randomly divided into two groups: T2DM NAFLD metformin group (T2DM NAFLD group), T2DM NAFLD group (C group), T2DM group (control group), 10 rats in each group (blank control group). The rats in group A were fed with high glucose and high fat diet for 4 weeks. Group C was fed with basic diet for 4 weeks. Group D was fed with basic diet for 4 weeks. The model of T2DM was established by intraperitoneal injection of STZ in group C of basal feed for 8 weeks. After 4 weeks, group A was given metformin 150 mg/(kg d) for 4 weeks. Group D was given the same amount of normal saline for 4 weeks. After the intervention, blood samples were collected from abdominal aorta of the anesthetized rats, and the serum TNF- 伪 IL-6 levels and the levels of serum TNF- 伪 IL-6 were measured. Liver tissue was taken and liver index was calculated. The histopathological changes of liver were observed by HE staining. The expression of TNF- 伪-6-6 protein in liver tissue was detected by immunohistochemical method and Western blotting method. Results the levels of serum TNF- 伪 IL-6 were higher in group C than those in group D (P 0.05 or 0.01). Group A was lower than that in group B (P 0.05 or 0.01). The level of serum TNF- 伪 IL-6 in group B was higher than that in group B (P 0.05 or 0.01). The level of IL-6 in group A was lower than that in group B (P 0.05 or 0.01). When the liver index of group D was lower than that of group B (P < 0.01), the liver structure of group D was intact. The hepatic lobule structure was normal. In some cases, the degree of steatosis and the infiltration of inflammatory cells in the liver of group A were significantly lower than those in group B (P < 0.05). The expression of TNF- 伪 and IL-6 protein in group C was significantly higher than that in group D (P = 0.01) and the expression of TNF- 伪 -IL-6 in group A was lower than that in group B (P < 0.05). Conclusion metformin can obviously improve the liver function and inhibit the development of NAFLD in T2DM combined with NAFLD rats, and its mechanism may be to improve the chronic inflammatory state by reducing the expression of inflammatory factors, thus exerting the protective effect of liver.
【作者单位】：沈阳医学院附属中心医院;中国医科大学附属盛京医院;
【基金】：辽宁省沈阳市科技计划项目(F14-158-9-29)
【分类号】：R575.2;R587.1

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