中药筋脉通胶囊通过增强血红素加氧酶-1/一氧化碳系统活性改善链脲佐菌素诱导的糖尿病大鼠周围神经病变的实验观察

Jinmaitong capsule can ameliorate the peripheral neuropathy of STZ-DM rats by enhancing the activity of HO-1/CO

目的观察中药筋脉通胶囊对STZ诱导的糖尿病大鼠坐骨神经血红素加氧酶-1(HO-1)、半胱氨酸天冬氨酸酶3(Caspase-3)的表达,以及对血浆一氧化碳(CO)含量的影响。方法腹腔内注射STZ诱导建立糖尿病大鼠模型,随机分为模型(DM)组,筋脉通低(JMT-L)、中(JMT-M)和高剂量(JMTH)组,以及硫辛酸(TAC)组,另设立正常对照(NC)组。成模后1次/d灌胃给药,共12周。电子Von Frey仪检测机械痛阈值,免疫组织化学法检测坐骨神经HO-1和Caspase-3蛋白表达,RT-PCR检测相应mRNA表达,并检测血浆一氧化碳血红蛋白(COHb)含量。结果与NC组比较,其他各组机械痛阈值、COHb含量,以及坐骨神经HO-1蛋白及其mRNA表达水平下降(P<0.01),Caspase-3蛋白及其mRNA表达水平升高(P<0.01)。与DM组比较,筋脉通各组机械痛阈值、血浆COHb含量,以及坐骨神经HO-1蛋白及其mRNA表达水平升高(P<0.01),Caspase-3蛋白及其mRNA表达水平降低(P<0.01);JMT-M组提高机械痛阈值、坐骨神经HO-1蛋白表达及降低坐骨神经Caspase-3蛋白表达优于TAC组(P<0.05或P<0.01)。结论筋脉通胶囊可通过增强HO-1/CO系统活性,降低Caspase-3水平,改善大鼠糖尿病周围神经病变。

Objective To observe the effects of Jinmaitong capsule （JMT） on the expressions of haem oxygenase-l （HO-1） and caspase-3 in sciatic nerve and the level of plasma carbon monoxide （CO） in ST-induced diabetic rats. Methods Diabetic rat model was built by intraperitoneal injection of STZ. All the diabetic rats were randomly divided into five groups, diabetic model group （DM）, low-dose JMT group （JMT-L）, middle-dose JMT group （JMT-M）, high-dose JMT group （JMT-H） and thioctic acid capsule group （TAC）. Normal rats served as normal control group （NC）. All rats were treated with intragastric administration of drugs once daily for 12 weeks. The mechanical withdrawal threshold was tested by electronic Von Frey instrument. The expression of HO-1 and caspase-3 and their mRNAs in sciatic nerve were detected by SABC immunohistochemical method and real-time fluorogenetic quantitative PCR respectively. The content of plasma COHb was also measured. Results The mechanical withdrawal threshold, the content of plasma COHb and the expression of HO-1 and HO-1 mRNA of sciaticnerve decreased significantly in DM groups than NC group （P〈0.01）. The mechanical withdrawal threshold, the content of plasma COHb and the expression of HO-1 and HO-1 mRNA of sciatic nerve were higher in JMT groups than DM group （P〈0.01）. JMT-M group was significantly better than TAC group in increasing the mechanical withdrawal threshold, enhancing expression of HO-1 of sciatic nerve, and decreasing the expression of caspase-3 （P〈0.05 or P〉0. 01）. Conclusion Jinmaitong capsule can improve the peripheral neuropathy of STZ-DM rats by enhancing the activity of HO-1/CO, and decreasing the level of caspase-3.