黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关Bax和Caspase-12的影响  

Effect of Modified Huangqi Guizhi Wuwutang on Apoptosis-related Bax and Caspase-12 of Sciatic Nerve Cells in Diabetes Rats

作　　者：张岩[1] 龙泓竹[2] 王曦鹏 曹伟芳 吴丽丽 刘铜华 周静鑫[6] ZHANG Yan;LONG Hongzhu;WANG Xipeng;CAO Weifang;WU Lili;LIU Tonghua;ZHOU Jingxin(Beijing Friendship Hospital Affiliated to Capital Medical University,Beijing 100050,China;The Second Department of Pulmonary Diseases of China-Japan Friendship Hospital,Beijing 100029,China;Hospital of Beijing International Studies University,Beijing 100024,China;Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing 100007,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]首都医科大学附属北京友谊医院,北京100050 [2]中日友好医院中医肺病二部,北京100029 [3]北京第二外国语学院校医院,北京100024 [4]中国医学科学院基础医学研究所,北京100007 [5]北京中医药大学中医学院,北京100029 [6]北京中医药大学东直门医院,北京100700

出　　处：《中国实验方剂学杂志》2023年第16期58-64,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81804091)。

摘　　要：目的:研究黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关B细胞淋巴瘤-2相关X蛋白(Bax)和胱天蛋白酶-12(Caspase-12)蛋白与mRNA表达的影响,以探究黄芪桂枝五物汤加减治疗糖尿病周围神经病变的作用机制。方法:选用动物实验方法进行研究,将60只雄性SD大鼠通过高糖高脂饲料喂养联合链尿佐菌素(STZ)腹腔注射诱导成糖尿病大鼠动物模型,连续3 d随机血糖≥16.7 mmol·L^(-1)者为糖尿病大鼠造模成功,将48只造模成功的糖尿病大鼠随机分为模型组、α-硫辛酸组(0.026 8 g·kg^(-1)·d^(-1))、中药高、低剂量组(2.5、1.25 g·kg^(-1)·d^(-1)),每组各12只,并设正常组10只。监测大鼠体质量和随机血糖水平;干预16周末通过Key point肌电采集系统检测大鼠坐骨神经传导速度;分别通过蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠坐骨神经中Bax和Caspase-12蛋白与mRNA的表达。结果:与正常组比较,模型组大鼠体质量显著下降(P<0.01),随机血糖水平显著升高(P<0.01);干预16周,与模型组比较,中药高剂量组大鼠体质量明显升高(P<0.05),其他给药组体质量变化差异无统计学意义;各给药组随机血糖水平均显著降低(P<0.01)。与正常组比较,干预16周,模型组大鼠运动和感觉神经传导速度显著降低(P<0.01);与模型组比较,各给药组大鼠运动和感觉神经传导速度均明显升高(P<0.05,P<0.01)。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12蛋白表达显著升高(P<0.01);与模型组比较,各给药组大鼠坐骨神经Bax和Caspase-12蛋白表达均显著降低(P<0.01)。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12 mRNA表达显著升高(P<0.01);与模型组比较,α-硫辛酸组、中药高剂量组大鼠坐骨神经Bax mRNA表达明显降低(P<0.05,P<0.01),中药低剂量组坐骨神经Bax mRNA表达降低有下降趋势;各给药组大鼠坐骨神经Caspase-12 mRNA�Objective:To investigate the effect of modified Huangqi Guizhi Wuwutang(MHGW)on the protein and mRNA expression of B-cell lymphoma-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-12(Caspase-12)related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes.Method:Animal experiments were conducted.A diabetes model was induced in sixty male sprague-dawley(SD)rats by feeding on a high-sugar and high-fat diet combined with streptozotocin(STZ)intraperitoneal injection.Rats with random blood glucose levels≥16.7 mmol·L^(-1) for three consecutive days were considered to have successfully developed diabetes.Forty-eight rats that successfully developed diabetes were randomly divided into a model group,anα-lipoic acid group(0.0268 g·kg^(-1)·d^(-1)),a high-dose MHGW group(2.5 g·kg^(-1)·d^(-1)),and a low-dose MHGW group(1.25 g·kg^(-1)·d^(-1)),with 12 rats in each group.Another 10 rats were assigned to the normal group.Body weight and random blood glucose levels of the rats were monitored.At the end of a 16-week intervention period,the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system.The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction(Real-time PCR),respectively.Result:Compared with the normal group,the model group showed a significant decrease in body weight(P<0.01)and a significant increase in random blood glucose levels(P<0.01).After a 16-week intervention,compared with the model group,the high-dose MHGW group exhibited a significant increase in body weight(P<0.05),while there were no statistically significant differences in body weight changes among the other treatment groups.Random blood glucose levels significantly decreased in all treatment groups(P<0.01).After 16 weeks of intervention,compared with the normal group,the

关 键 词：黄芪桂枝五物汤加减 糖尿病周围神经病变 细胞凋亡 B细胞淋巴瘤-2相关X蛋白 胱天蛋白酶-12 

分 类 号：R2-0[医药卫生—中医学] R22R242R2-031R285.5