摘要
目的初步探究二甲双胍(MET)对大鼠肝癌血管形成影响及其作用机制。方法60只Wistar大鼠,按照随机数字表法分为对照组、模型组MET低剂量组(10 mgkg)、MET中剂量组(20 mg/kg)、MET高剂量组(40 mg/kg)、阳性对照药组,每组10只,腹腔注射二乙基亚硝铵(DEN)诱导大鼠肝癌模型,苏木素-伊红(HE)染色观察各组大鼠肝脏组织形态学变化;酶联吸附法(ELISA)测定各组大鼠血清中VEGF含量以及肝功能指标(ALT、AST、ALP和TBIL等);免疫组化检测肝组织VEGF阳性表达情况;蛋白质免疫印迹法(Westerm bloting)检测各组大鼠肝组织IL-6、p-STAT3蛋白表达。结果与对照组相比,模型组大鼠肝组织多处坏死,伴有明显的形态异常,血清VEGF、ALT、AST、ALP和TBIL含量均显著性升高(均P<0.01),肝组织IL-6、p-STAT3蛋白表达均显著性升高(均P<0.01),VEGF蛋白阳性表达率升高(均P<0.01)。与模型组相比,MET不同剂量处理组肝组织坏死减轻,细胞变性程度减轻,VEGF、ALT、AST、ALP和TBIL,均含量降低(P<0.05或P<0.01),IL6、p-STAT3蛋白表达显著性降低(P<0.05或P<0.01),VEGF蛋白阳性表达率降低(P<0.01)。结论MET能够抑制大鼠肝癌血管生成,其机制可能与抑制IL-6/STAT3信号通路降低VEGF表达相关。
Objective To preliminarily explore the effect of metformin(MET)on the angiogenesis of liver cancer in rats and its mechanism.Methods 60 Wistar rats were divided into control group,model group,MET low-dose group(10 mg/kg),MET medium-dose group(20 mg/kg),and MET high-dose group(40 mg/kg)according to the random number table method,kg),positive control group,10 rats in each group,intraperitoneal injection of diethyl nitrite(DEN)to induce rat liver cancer model,hematoxylin-eosin(HE)staining to observe the morphological changes of rat liver tissue in each group;enzymes ELISA was used to determine the serum VEGF content and liver function indexes(ALT,AST,ALP,TBIL,etc.)of rats in each group;immunohistochemistry to detect the positive expression of VEGF in liver tissue;The expression of IL-6 and p-STAT3 protein in liver tissue of rats in each group by Western blotting;.Results Compared with the control group,the rats in the model group had multiple necrosis in liver tissues,accompanied by obvious morphological abnormalities.The serum VEGF,ALT,AST,ALP and TBIL levels were significantly increased(all P<0.01),and the liver tissue IL-6.The expression of p-STAT3 protein increased significantly(all P<0.01),and the positive expression rate of VEGF protein increased(all P<0.01).Compared with the model group,the different doses of MET treatment group reduced liver tissue necrosis,reduced cell degeneration,decreased VEGF,ALT,AST,ALP and TBIL levels(P<0.05 or P<0.01),IL-6,p-STAT3 The protein expression decreased significantly(P<0.05 or P<0.01),and the positive expression rate of VEGF protein decreased(P<0.01).Conclusion MET can inhibit the angiogenesis of liver cancer in rats,and its mechanism may be related to inhibiting IL-6/STAT3 signaling pathway and reducing the expression of VEGF.
作者
陈冠吉
王春燕
CHEN Guan-ji;WANG Chun-yan(Zhangjiagang Hospital of Traditional Chinese Medicine,Zhangjiagang 215600,China)
出处
《肝胆外科杂志》
2022年第2期149-153,共5页
Journal of Hepatobiliary Surgery
