抵当汤对糖尿病大鼠心肌组织JAK2/STAT3信号通路的影响

Effect of Didang Decoction on Myocardial JAK2/STAT3 Pathway in Diabetic Rats

目的探讨抵当汤及其拆方对糖尿病大鼠肥大心肌细胞JAK2/STAT 3信号通路的影响。方法单次注射链脲佐菌素复制糖尿病大鼠模型,将糖尿病大鼠随机分为模型组、抵当汤组、桃仁大黄组、水蛭虻虫组和缬沙坦组,以正常雄性SD大鼠作为正常对照组。正常对照组和模型组给予蒸馏水灌胃,其余各组大鼠接受相应药物灌胃,连续8周。采用Western blot法检测心钠素(atrial natriuretic peptide,ANP)、心肌组织JAK2和STAT3蛋白表达,采用实时荧光定量PCR法检测JAK2、STAT3mRNA表达。结果与正常对照组比较,模型组ANP、JAK2、STAT3蛋白以及JAK2、STAT3mRNA表达水平均显著上调(P<0.05)。水蛭虻虫拆方和桃仁大黄拆方对糖尿病大鼠心肌组织ANP、JAK2和STAT3蛋白表达的主效应均具有统计学意义(P<0.05),两者的交互作用均无统计学意义(P>0.05)。水蛭虻虫拆方和桃仁大黄拆方对糖尿病大鼠心肌组织JAK2、STAT3mRNA表达的交互作用具有统计学意义(P<0.05)。缬沙坦组、抵当汤组及两个抵当汤拆方组ANP、JAK2蛋白及JAK2 mRNA表达水平比较,差异具有统计学意义(P<0.05)。结论抵当汤延缓糖尿病大鼠心肌细胞肥大的机制与抑制JAK2/STAT3信号通路有关,其拆方对JAK2、STAT3mRNA表达的效应存在相互影响。

Objective To investigate the effect of Didang Decoction and its separated recipes on the JAK2/STAT3 pathway in hypertrophic cardiomyocytes in diabetic rats. Methods A rat model of diabetes was established with a single injection of streptozotocin （STZ）. The diabetic rats were randomly divided into model group, Didang Decoction group, Taoren Dahuang group, leech-gadfly group, and valsartan group, and normal male Sprague-Dawley rats were used as normal control group. The rats in the normal control group and model group were given distilled water by gavage, and those in the other groups were given corresponding drugs by gavage for 8 weeks continuously. Western blot was used to measure atrial natriuretic peptide （ANP） level and the protein expression of JAK2 and STAT3 in the myocardium, and quantitative real-time PCR was used to measure the mRNA expression of JAK2 and STAT3. Results Compared with the normal control group, the model group showed significantly upregulated ANP level and protein and mRNA expression of JAK2 and Taoren Dahuang recipe showed significant main effects STAT3 （P〈0.05）. The leech-gadfly recipe and on ANP level and the protein expression of JAK2 and STAT3 in the myocardium of diabetic rats （P〈0.05）, but the interaction between the two recipes was not significant （P〈0.05）. The leech-gadfly recipe and Taoren Dahuang recipe showed a significant inter- action in regulating the mRNA expression of JAK2 and STAT3 in the myocardium of diabetic rats （P〈 0.05）. The ANP level and the mRNA and protein expression of JAK2 showed significant differences between the valsartan group, Didang Decoction group, Taoren Dahuang group, and leech-gadfly group （P% 0.05）. Conclusion The mechanism of action of Didang Decoction in delaying cardiomyocyte hypertrophy in diabetic rats may be related to its inhibitory effect on the JAK2/STAT3 pathway, and the Separated reci- pes of Didang Decoction interact with each other in regulating the mRNA expression of JAK2 and STAT3.