目的 研究白藜芦醇对糖尿病肾病大鼠JAK/STAT信号通路的影响.方法 高糖高脂饲料喂养健康SD大鼠8周后,用链脲佐菌素45 mg/kg腹腔注射造模.将40只成模大鼠随机分为模型组、白藜芦醇低剂量组、白藜芦醇中剂量组、白藜芦醇高剂量组,每组10只.白藜芦醇低、中、高剂量组分别给予10 mg/kg、20 mg/kg、40 mg/kg白藜芦醇灌胃治疗,正常组和模型组则给予等容量蒸馏水.连续灌胃4周后,以HE染色观察肾脏组织形态学改变,并比较各组大鼠血糖、血清胆固醇、甘油三酯、尿素氮和肌酐水平.采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)和白介素-6(interleukin-6,IL-6)水平;荧光定量PCR法检测肾组织两面神激酶2(Janus kinase 2,JAK2)、信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)、细胞因 子信号抑制物 1(suppressor of cytokine signaling 1,SOCS1)、ICAM-1和IL-6的mRNA水平;Western blot法检测肾组织磷酸化两面神激酶2(phosphorylated Janus kinase 2,p-JAK2)、磷酸化信号传导与 转录激活因子 3(phosphorylated signal transducer and activator of transcription 3,p-STAT3)、SOCS1、ICAM-1 和 IL-6 的蛋白表达.结果 经白藜芦醇治疗后,白藜芦醇各剂量组肾脏病理损伤减轻.与正常组比较,模型组大鼠血糖、血清胆固醇、甘油三酯、尿素氮、肌酐均升高(P均＜0.05).与模型组相比,白藜芦醇中、高剂量组大鼠血糖、血清胆固醇、甘油三酯、尿素氮和肌酐均降低(P均＜0.05).白藜芦醇各剂量组大鼠血清ICAM-1和IL-6均较模型组显著降低(P均＜0.05),且白藜芦醇中、高剂量组大鼠血清ICAM-1和IL-6显著低于低剂量组(P均＜0.05).白藜芦醇各剂量组肾组织JAK2和STAT3的mRNA水平无明显变化(P＞0.05),而p-JAK2和p-STAT3的蛋白表达均较模型组下降(P均＜0.05);ICAM-1和IL-6的mRNA水平和蛋白表达均较模型组降低(P均＜0.05),而SOCS1的mRNA水平和蛋白表达均较模型组升高(P均＜0.05).结论 白藜芦醇能减轻糖尿病肾病大鼠的肾脏损害,控制其血糖、血脂,降低血清尿素氮和肌酐水平,其机制可能与抑制JAK/STAT信号通路有关.
Effects of Resveratrol on JAK/STAT Signaling Pathway in Diabetic Nephropathy Rats
Objective To study the effect of resveratrol on JAK/STAT signaling pathway in diabetic nephrop-athy rats.Methods After feeding healthy SD rats with high sugar and high fat feed for 8 weeks,streptozotocin 45 mg/kg was intraperitoneally injected to create a model.The model rats were randomly divided into the model group,low dose resveratrol group,medium dose resveratrol group,and high dose resveratrol group,with 10 rats in each group.The low,medium,and high dose groups of resveratrol were given 10 mg/kg,20 mg/kg,and 40 mg/kg of resveratrol,respectively.The normal group and model group were given equal volume distilled water by ga-vage.After continuous gavage for 4 weeks,HE staining was used to observe the morphological changes in renal tis-sue,and the levels of blood glucose,serum cholesterol,triglyceride,urea nitrogen and creatinine in each group of rats were compared.The serum levels of intercellular adhesion molecule-1(ICAM-1)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),suppressor of cytokine signaling 1(SOCS1),ICAM-1 and IL-6 in renal tissue were detected by fluorescence quantitative PCR.The protein expression of phosphorylated Janus ki-nase 2(p-J AK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3),SOCS1,ICAM-1 and IL-6 in renal tissue were detected by Western blot.Results After treatment with resveratrol,renal pathologi-cal damage was reduced in each dose group of resveratrol.Compared with the normal group,the blood glucose,ser-um cholesterol,triglyceride,urea nitrogen and creatinine of rats in the model groups were all increased(all P＜0.05).Compared with the model group,the blood glucose,serum cholesterol,triglyceride,urea nitrogen and creati-nine of rats in the medium and high dose groups of resveratrol were all reduced(all P＜0.05).The serum levels of ICAM-1 and IL-6 in each dose group of resveratrol were significantly reduced compared to the model group(all P＜0.05),and the serum levels of ICAM-1 and IL-6 in the medium and high dose groups of resveratrol were signifi-cantly lower than those in the low dose group(all P＜0.05).The mRNA levels of JAK2 and STAT3 in renal tissue of each dose group of resveratrol showed no significant changes(P＞0.05),while the protein expression of p-JAK2 and p-STAT3 were decreased compared to the model group(all P＜0.05).The mRNA levels and protein expres-sion of ICAM-1 and IL-6 in each dose group of resveratrol were all lower than those of the model group(all P＜0.05),while the mRNA levels and protein expression of SOCS1 were increased compared to the model group(all P＜0.05).Conclusion Resveratrol could alleviate the renal damage of diabetic nephropathy rats,control the blood glucose and lipid,and reduce serum urea nitrogen and creatinine levels,and its mechanism may be related to the in-hibition of JAK/STAT signaling pathway.
万方数据
维普
