黄芪桂枝五物汤不同剂量治疗糖尿病周围神经病变量效关系及对经典Wnt信号通路的影响

Dose-response relationship of different doses of Huangqi Guizhi Wuwu Decoction in the treatment of diabetic peripheral neuropathy and their influence on classic Wnt signaling pathway

目的观察《金匮要略》黄芪桂枝五物汤原方不同给药剂量治疗糖尿病周围神经病变气虚血瘀证的疗效及对经典Wnt信号通路的影响。方法将2018年4月—2020年12月嘉定区中医医院收治的120例糖尿病周围神经病变患者随机分为甲钴胺组、中药低剂量组、中药正常剂量组、中药高剂量组,每组30例。甲钴胺组给予甲钴胺口服,中药正常剂量组给予原方剂量黄芪桂枝五物汤口服,中药低、高剂量组分别给予0.5倍和1.5倍原方剂量黄芪桂枝五物汤口服,4组均治疗12周。观察比较4组治疗前后糖代谢指标[空腹血糖(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)]、多伦多临床神经病变评分量表(TCSS)评分、中医症状积分、腓总神经和正中神经的运动神经传导速度(MNVC)及感觉神经传导速度(SNVC)、血清中经典Wnt信号通路关键分子(β-catenin、cyclinD1、c-myc、DKK1)mRNA表达量,统计4组临床疗效及达到显效、有效的时间。结果治疗后,中药正常剂量组和中药高剂量组FPG、2hPG、HbA1c、TCSS评分、中医症状积分及血清中DKK1 mRNA表达量均明显低于甲钴胺组(P均<0.05),血清中β-catenin、cyclinD1、c-myc mRNA表达量均明显高于甲钴胺组(P均<0.05),腓总神经和正中神经MNVC、SNVC均明显快于甲钴胺组(P均<0.05);中药正常剂量组和中药高剂量组总有效率分别为90.0%(27/30)和93.3%(28/30),均明显高于甲钴胺组的63.3%(19/30),且达到显效、有效的时间均明显短于甲钴胺组,差异均有统计学意义(P均<0.05)。结论黄芪桂枝五物汤原方剂量和1.5倍原方剂量治疗糖尿病周围神经病变气虚血瘀证疗效优于甲钴胺,且疗效呈剂量依赖性提高,其作用机制可能与激活经典Wnt信号通路有关。

Objective It is to observe the therapeutic effect of different dosage of Huangqi Guizhi Wuwu Decoction in the“Synopsis of the Golden Chamber”on diabetic peripheral neuropathy(DPN)of qi deficiency and blood stasis syndrome and its influence on classic Wnt signaling pathway.Method A total of 120 patients with DPN admitted to Jiading Hospital of Traditional Chinese Medicine from April 2018 to December 2020 were randomly divided into a mecobalamin group,a low-dose traditional Chinese medicine group,a normal-dose traditional Chinese medicine group,and a high-dose traditional Chinese medicine group,with 30 cases in each group.The mecobalamin group was given mecobalamin by oral administration,the normal dose traditional Chinese medicine group was given the original dose of Huangqi Guizhi Wuwu Decoction by oral administration,and the low and high dose groups of traditional Chinese medicine were respectively given 0.5 times and 1.5 times the original dose of Huangqi Guizhi Wuwu Decoction orally,all the four groups were treated for 12 weeks.The glucose metabolism indicators[fasting plasma glucose(FPG),2 h postprandial plasma glucose(2hPG),glycosylated hemoglobin(HbA1c)],scores of Toronto Clinical Scoring System(TCSS),scores of traditional Chinese medical symptom,motor nerve conduction velocity(MCV)and sensory nerve conduction velocity(SCV)of common peroneal nerve and median nerves,the mRNA expression of key molecules of the classic Wnt signaling pathway(β-catenin,cyclinD1,c-myc,DKK1)in serum in the four groups were observed and compared before and after treatment.Results After treatment,the FPG,2hPG,HbA1c,TCSS scores,traditional Chinese medical symptom scores and serum DKK1 mRNA expression in the normal dose group and high dose group of traditional Chinese medicine were significantly lower than those in the mecobalamin group(all P<0.05),the mRNA expressions of catenin,cyclinD1 and c-myc in serum were significantly higher than those in the mecobalamin group(all P<0.05),and the MCV and SCV of the common peroneal nerve and median nerve were significantly faster than those in the mecobalamin group(all P<0.05).The total effective rates of the normal dose group and high dose group of traditional Chinese medicine respectively were 90.0%(27/30)and 93.3%(28/30),which were significantly higher than 63.3%(19/30)of the methylcobalamin group,and the time to achieve marked effect and effective effect was significantly shorter than that of the methylcobalamin group,and the differences were statistically significant(all P<0.05).Conclusion The original dose of Qiguizhi Wuwu Decoction and 1.5 times the original dose of the decoction were more effective than mecobalamin in treating DPN with Qi deficiency and blood stasis syndrome,and the efficacy was increased in a dose-dependent manner.The mechanism of action may be related to the activation of the classic Wnt signaling pathway.