筋脉通胶囊对糖尿病大鼠坐骨神经神经生长因子受体p75NTR及TrkA表达的影响

Effects of Jinmaitong Capsule on the expressions of nerve growth factor receptor p75NTR and TrkA of sciatic nerve in diabetic rats

目的观察中药筋脉通胶囊对链脲佐菌素(STZ)诱导的糖尿病(DM)大鼠坐骨神经神经生长因子(NGF)受体p75神经营养因子受体(p75NTR)和酪氨酸激酶A(TrkA)表达的影响。方法用STZ诱导建立DM大鼠模型,随机分为模型(DM)组,筋脉通低、中和高剂量(JMTL、JMTM、JMTH)组,神经妥乐平(Ntp)组,并设立正常对照(NC)组。成模后即灌胃给药,JMTL、JMTM、JMTH组分别按成人剂量的5、10和20倍给药,Ntp组按成人剂量的10倍给药,持续16周。处死前检测热水甩尾试验和机械痛阈值,免疫组化法检测坐骨神经p75NTR和TrkA的表达。结果与NC组相比,DM组和各治疗组的甩尾潜伏期延长,DM组和JMTH组的机械痛阈值显著降低,DM组和各治疗组p75NTR和TrkA表达下降(P<0.05或P<0.01)。与DM组相比,JMTL、JMTM与Ntp组的甩尾潜伏期显著缩短、机械痛阈值显著升高,各治疗组的p75NTR和TrkA表达均显著升高(P<0.05或P<0.01)。JMTM、JMTH组的p75NTR表达较Ntp组显著升高(P<0.05)。结论筋脉通胶囊可通过增强坐骨神经NGF受体p75NTR和TrkA的表达,改善糖尿病大鼠的周围神经病变。

ABSTRACT Objective To study the effects of Chinese medicine Jinmaitong Capsule （JMT） on the expressions of nerve growth factor （NGF） receptor, p75 neurotrophin receptor （NTR） and tyrosine kinase A （TrkA） of sciatic nerve in streptozotocin （STZ）-induced rats with diabetes mellitus （DM）. Method DM rat models were established by STZ, which were randomly divided into 5 groups including a model （DM） group, a low-, medium- and high-dose of JMT （JMTL, JMTM, JMTH） group, and a Neurotropin （Ntp） group. Meanwhile, a normal control （NC） group was set up. The intragastric administration was applied for 16 weeks after modeling, and the JMTL, JMTM, JMTH groups were respectively given by quintupling, decuple and twentyfold dose of adult recommended dosage, while the Ntp group was treated with decuple dose. The hydrothermal tail-flick and mechanical withdrawal threshold were carried out before sacrificing. The expressions of p75NTR and TrkA in sciatic nerve were detected by immunohistochemistry （IHC）. Results Compared with the NC group, the tail-flick latency prolonged and the expressions of p75NTR and TrkA decreased in the DM and each treatment groups, and the mechanical withdrawal threshold obviously decreased in the DM and JMTH groups （P 〈0.05 or P 〈0,01）. Compared with the DM group, the tail-flick latency significantly shortened and the mechanical withdrawal threshold apparently increased in the JMTL, JMT-M and Ntp groups （P 〈0.05）, the expressions of p75NTR and TrkA were all increased obviously in all the treatment groups （P 〈0.05 or P 〈0.01）. The expression of p75NTR in the JMTM and JMTH groups was significantly enhanced when compared with the Ntp group （P 〈0.05）. Conclusion Jinmaltong Capsule could ameliorate the peripheral neuropathy of DM rats by enhancing the expressions of NGF receptor p74NTR and TrkA in sciatic nerve.