益肾胶囊对糖尿病肾病大鼠肾组织JAK/STAT信号通路及α-SMA、FN的影响

Effect of Yishen Capsule on JAK/STAT Signaling Pathway α-SMA, FN Expression in Rats with Diabetic Nephropathy

目的:探讨益肾胶囊对糖尿病肾病(DN)大鼠24h尿蛋白定量、尿素氮(BUN)、血肌酐(Scr)、JAK/STAT及α-平滑肌激动蛋白(α-SMA)、纤维连接蛋白(FN)的影响及其机制。方法:SD大鼠55只,随机留取10只为正常对照组(N)。利用一次性腹腔注射链脲佐菌素的方法建立DN大鼠模型。造模成功大鼠按随机数字表法分为糖尿病肾病模型组(DN)、益肾胶囊治疗组(DN+Y)、氯沙坦钾治疗组(DN+L)、氯沙坦钾+益肾胶囊治疗组(DN+L+Y),每组10只,连续灌胃12周。于实验的12周检测24h尿蛋白定量;12周末处死大鼠,检测血糖、BUN、Scr;取大鼠肾组织做组织病理学观察;免疫组化法检测肾组织磷酸化JAK2(p-JAK2)、磷酸化STAT3(p-STAT3)、α-SMA、FN的表达。结果:实验12周末,与DN组比较,益肾胶囊治疗组24h尿蛋白定量、BUN、Scr明显降低(P<0.05),肾组织形态学改变较轻,p-JAK2、p-STAT3、α-SMA、FN的表达显著降低(P<0.05)。氯沙坦钾联合益肾胶囊治疗组与氯沙坦钾治疗组比较,差异有统计学意义(P<0.05)。结论:益肾胶囊可能通过抑制糖尿病肾病大鼠肾组织JAK/STAT信号通路的活化,下调α-SMA、FN的表达,延缓了糖尿病肾病的进展;益肾胶囊联合氯沙坦钾可更好地保护肾脏功能,提示二者联合使用有协同作用。

Objective： To observe the effect and mechanism of Yishen capsule on urinary protein/24 h, blood urea nitrogen （BUN）, serum creatinine （Scr） and JAK/STAT, α-smooth muscle actin （α-SMA）, fibronectin （FN） in rats with diabetic nephropathy. Methods：55 SD rats, Random samples from 10 SD rats male as the normal control group （N）. The successful rat models were selected and randomly divided into four groups： diabetic nephropathic model group, yishen capsule group, Losartan Potassium Tablets group and yishen capsule combined with Losartan Potassium Tablets group, 10 rats each group. The DN models were induced by one intraperitoneal injection of streptozotocin（STZ）. All the rats received daily gavages for 12 weeks. The blood glucose（Glu）, urinary protein/24h, BUN and Scr were measured after 12weeks in each group respectively. The renal tissue pathological changes were observed under light microscope. The expression of the p-JAK2, p-STAT3, α-SMA and FN was measured by immunohistochemistry on kidney tissue. Results：At the end of 12 weeks, compared with model group, the urinary protein/24 h, BUN and Scr was reduced （P〈0.05）, Changes of renal morphology in light, the expression level of p-JAK2, p-STAT3, α-SMA and FN in the renal glomerulus were decreased （P〈0.05）. The difference between DN＋L＋Y and DN＋Y was statistically significant. Conclusion：Yishen Capsule may be through the activation inhibition of diabetic nephropathy rats JAK/STAT signaling pathway, reduce the expression of α –SMA and FN, delaying the progression of diabetic nephropathy. Yishen Capsule combined with losartan potassium could protect renal function better, suggesting that the combined use of the two drugs have synergistic effect.