抑制AngⅡ受体对糖尿病肾病的作用及JAK2/STAT3/SOCS1通路的影响

Effects of AngⅡreceptor on protection of diabetic nephropathy and JAK2/STAT3/SOCS1 pathway

目的 探究通过抑制AngⅡ受体调控JAK2/STAT3/SOCS1信号通路对糖尿病肾病肾组织的保护机制。方法 将大鼠随机分为NC组(不做任何干预,正常饲养,灌胃等体积的生理盐水干预)、DN组(糖尿病肾病大鼠模型组,灌胃等体积的生理盐水干预)和ARB组(DN组基础上灌胃40 mg/kg.d缬沙坦干预治疗),每组10只;药物干预第8周末,分别用全自动生化分析仪检测大鼠空腹血糖(FBG)、三酰甘油(TG)、血肌酐(Scr)及血尿素氮(BUN)水平,检测24 h尿蛋白总量(24 hUTP)、24 h尿微量白蛋白(24 h UmALB)水平,HE染色检测肾皮质组织病理学变化,蛋白质印迹法检测肾皮质组织匀浆中JAK2、p-JAK2、STAT3、p-STAT3及SOCS1蛋白表达。结果 DN组大鼠FPG、TG、Scr、BUN、UmALB及UTP水平均高于NC组,差异有统计学意义(P<0.05);与DN组比较,ARB组大鼠FPG、TG、Scr、BUN、UmALB及UTP水平显著降低,差异有统计学意义(P<0.05);与NC组比较,DN组大鼠肾小球体积增加,系膜细胞数量变多,肾小球上皮细胞形成大量空泡;与DN组比较,ARB组大鼠肾小球形态区域正常,基底膜轻微增生,肾小管排列区域整齐,病变程度模型减轻;与NC组比较,DN组大鼠肾皮质组织匀浆中p-JAK2/JAK2比值和p-STAT3/STAT3比值明显升高,SOCS1蛋白表达显著增加(P<0.05);与DN组比较,ARB组大鼠肾皮质组织匀浆中p-JAK2/JAK2比值和p-STAT3/STAT3比值显著降低,SOCS1蛋白表达显著升高(P<0.05)。结论 AngⅡ受体拮抗剂能减轻糖尿病肾病大鼠肾损伤,影响JAK2/STAT3/SOCS1蛋白的表达水平,对肾脏组织有保护作用。

Objective To investigate the protective mechanism of inhibiting angiotensin Ⅱ(AngⅡ)receptor on diabetic nephropathy by regulating JAK2/STAT3/SOCS1 signaling pathway.Methods Ratswere randomly divided into NC group( no intervention, normal feeding, intervention with an equalvolume of normal saline), DN group( diabetic nephropathy rat model group, intragastricadministration with an equal volume of normal saline) and ARB group( intervention treatment with40 mg/kg/d valsartan by gavage on the basis of DN group), 10 rats in each group.At the end of the8th week of drug intervention, the biochemical indexes[fasting blood glucose(FBG), triacylglycerol(TG), serum creatinine( Scr), blood urea nitrogen( BUN)] levels of the rats were detected byautomatic biochemical analyzer respectively;24-hour total urine protein(24 hUTP), 24 h urinarymicroalbumin(24 h UmALB) levels were tested;HE staining was used to detect the histopathologicalchanges of renal cortex;western blotting was used to detect JAK2, p-JAK2, STAT3, p-STAT3,SOCS1 protein expression.Results The levels of FPG, TG, Scr, BUN, UmALB, and UTP in the DN group were higher than those of NC group, differences were statistically significant(P< 0.05);compared with the DN group, the levels of FPG, TG, Scr, BUN, UmALB and UTP in the ARB groupsignificantly reduced, differences were statistically significant(P< 0.05).Compared with the NCgroup, the volume of the glomerulus in the model group increased, the number of mesangial cellsincreased, and the glomerular epithelial cells formed a large number of vacuoles;compared with DNgroup, the glomerular morphology of the ARB group was normal, basement membrane was slightlyhyperplastic;the renal tubules were arranged neatly, and the lesion model was reduced.Comparedwith the NC group, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio in the homogenate of renal cortextissue of DN group increased significantly, and the SOCS1 protein expression increased significantly(P< 0.05);compared with DN group, the ratio of p-JAK2/JAK2 and the ratio of p-STAT3/STAT3 inthe renal cortex of ARB group were significantly decreased, and the expression of SOCS1 protein wasincreased significantly(P< 0.05).Conclusion AngⅡ receptor antagonists can reduce renal injuryin rats with diabetic nephropathy, affecting the expression levels of JAK2/STAT3/SOCS1 proteins, andhaving protective effects on renal tissue.