益糖康调控JAK2/STAT3信号通路抑制炎症预防糖尿病肾病的研究

Study on Yitangkang(益糖康)Inhibiting Inflammation and Preventing Diabetic Nephropathy via Regulating JAK2/STAT3 Signal Pathway

目的基于JAK2/STAT3信号通路探讨益糖康对于糖尿病肾病的预防作用及其机制。方法SD雄性大鼠分为空白对照组、模型组、中药-低剂量组、中药-中剂量组、中药-高剂量组。模型组、中药-低剂量组、中药-中剂量组、中药-高剂量组大鼠高脂饲料喂养4周后,给予腹腔单次注射链脲佐菌素建立2型糖尿病模型,成模后中药低、中、高剂量组分别不同剂量中药复方益糖康干预;空白对照组普通饲料喂养并在其他组造模同时给予柠檬酸-柠檬酸钠缓冲液腹腔注射,蒸馏水灌胃。12周后取材,ELISA法检测糖化血红蛋白和肾脏组织炎症因子水平,qPCR检测肾脏组织炎症因子及JAK2、STAT3 mRNA表达,HE染色观察肾脏组织形态学改变。结果与空白对照组比较,模型组大鼠空腹血糖、糖化血红蛋白显著升高,肾脏组织形态见炎性浸润、基质增生,IL-1β、IL-2、IL-6、IL-10炎症因子水平显著升高,IL-1β、IL-6、JAK2、STAT3 mRNA表达显著上调;与模型组比较,中药-高剂量组可显著降低大鼠空腹血糖和糖化血红蛋白,改善肾脏组织形态,同时降低肾脏组织IL-1β、IL-2、IL-6水平,下调IL-1β、IL-6、JAK2、STAT3 mRNA表达。结论益糖康可能通过下调JAK2/STAT3信号通路抑制炎症预防糖尿病肾病的发生。

Objective To explore the preventive effect of Yitangkang(益糖康)on diabetic nephropathy and its mechanism based on the JAK2/STAT3 signaling pathway.Methods Male SD rats were divided into control group,model group,low dose-traditional Chinese medicine group,medium dose-traditional Chinese medicine group and high dose-traditional Chinese medicine group.Rats in the model group,low dose-traditional Chinese medicine group,medium dose-traditional Chinese medicine group and high dose-traditional Chinese medicine group were fed with high-fat diet for 4 weeks,and were given a single intraperitoneal injection of streptozotocin to establish type 2 diabetes models.The low,medium and high dose groups were treated with different doses of traditional Chinese medicine compound Yitangkang.The control group was fed with ordinary feed and given intraperitoneal injection of citric acid-sodium citrate buffer when the other groups’rats were injected streptozotocin,and distilled water was given intragastrically.After 12 weeks,rats were sacrificed and samples were collected.ELISA was used to detect glycosylated hemoglobin and renal tissue inflammatory factor levels.The qPCR was used to detect renal tissue inflammatory factors and JAK2 and STAT3 mRNA expressions,and HE staining was used to observe the morphological changes of kidney tissue.Results Compared with those of the control group,the fasting blood glucose and glycosylated hemoglobin of the model group were significantly increased.The kidney tissue morphology showed inflammatory infiltration,stromal hyperplasia and levels of IL-1β,IL-2,IL-6 and IL-10 were significantly increased.IL-1β,IL-6,JAK2 and STAT3 mRNA expression were significantly up-regulated.Compared with the model group,the high-dose traditional Chinese medicine group significantly lowered fasting blood glucose and glycosylated hemoglobin,showing a significant improvement in kidney tissue morphology,and reduced levels of IL-1β,IL-2 and IL-6 in kidney tissue,and down-regulated the expressions of IL-1β,IL-6,JAK2 and STAT3 mRNA.Conclusion Yitangkang may inhibit inflammation and prevent the occurrence of diabetic nephropathy via down-regulating the JAK2/STAT3 signaling pathway.