知葛通脉汤对糖尿病周围神经病变大鼠背根神经节MAPK / ERK通路的影响

Effect of Zhige Tongmai Decoction on MAPK / ERK Pathway in Dorsal Root Ganglia for Rats with Diabetic Peripheral Neuropathy

目的:研究知葛通脉汤对糖尿病周围神经病变背根神经节丝裂原活化蛋白激酶(MAPK)/细胞外调节蛋白激酶(ERK)通路的影响。方法:选取无特定病原体级SD雄性大鼠50只为研究对象,随机选取10只作为对照组,其余40只为研究组,随机分为四组:知葛通脉汤低、中、高剂量组:分别按照每日2.5g/kg、7.5g/kg、15g/kg体重标准灌胃知葛通脉汤,模型组灌胃给予等量生理盐水,连续给药6周,观察记录大鼠背根神经节中磷酸化p38MAPK(p-p38MAPK)、p38MAPK、ERK、磷酸化ERK(p-ERK)活性和表达水平以及p38MAPK、ERKmRNA水平。结果:模型组p-p38MAPK、p-ERK活性和蛋白表达水平明显高于对照组,差异有统计学意义(P<0.05);知葛通脉汤低、中、高剂量组p-p38MAPK、p-ERK活性和蛋白表达水平明显低于模型组(P<0.05);知葛通脉汤高剂量组p-p38MAPK、p-ERK活性和蛋白表达水平明显低于低剂量组(P<0.05),各组之间p38MAPK、ERK活性和蛋白表达水平无明显差异(P>0.05);模型组p38MAPK、ERKmRNA表达水平明显高于对照组,差异有统计学意义(P<0.05);知葛通脉汤低、中、高剂量组p38MAPK、ERKmRNA表达水平明显低于模型组(P<0.05);知葛通脉汤高剂量组p38MAPK、ERKmRNA表达水平明显低于低剂量组(P<0.05)。结论:知葛通脉汤可降低p-p38MAPK、p-ERK活性和蛋白表达水平,有效抑制背根神经节MAPK/ERK通路。

Objective:To investigate the effect of Zhige Tongmai Decoction on mitogen-activated protein kinase(MAPK)/extracellular regulatory protein kinase(ERK)pathway in diabetic peripheral neuropathy.Methods:Fifty male SD rats without specific pathogens were selected as subject.After 1 week of normal feeding,10 rats were randomly selected as controlled group,and the remaining 40 were randomly divided into four groups,each group consisting of 10 rats:Low,medium and high doses of broth:according to the daily 2.5 g/kg,7.5 g/kg,15 g/kg body weight,Zhige Tongmai Decoction was administered to the model group.The controlled group was given the same amount of normal saline by intragastric administration.Weekly,the phosphorylation of p38 MAPK(p-p38MAPK),p38MAPK,ERK,phosphorylated ERK(p-ERK)activity and expression levels,and p38MAPK and ERK mRNA levels in rat dorsal root ganglia were observed.Results:The p-p38MAPK,p-ERK activity and protein expression levels in the model group were significantly higher than those in the controlled group(P<0.05).The p-p38MAPK and p-ERK activities in the low,medium and high dose groups of Zhige Tongmai Decoction and the protein expression level was significantly lower than that of the model group(P<0.05).The p-p38MAPK,p-ERK activity and protein expression levels in the high dose group of ZhigeTongmai Decoction Group were significantly lower than those in the low dose group(P<0.05).There was no significant difference in ERK activity and protein expression level(P>0.05).The expression levels of p38MAPK and ERK mRNA in the model group were significantly higher than those in the controlled group,the difference was statistically significant(P<0.05).The expression level of p38MAPK and ERK mRNA of the low,medium and high dose group of Zhige Tongmai Decoction was significantly lower than that of the model group(P<0.05).The expression of p38MAPK and ERK mRNA in the high dose of Zhige Tongmai Decoction group was significantly lower than that in the low dose group(P<0.05).Conclusion:Zhige Tongmai Decoction can reduce the activity of p-p38MAPK,p-ERK and protein,and effectively inhibit the MAPK/ERK pathway of dorsal root ganglia.