筋脉通胶囊对糖尿病大鼠周围神经内质网应激的影响

Effects of Jinmaitong Capsule on Endoplasmic Reticulum Stress in Peripheral Nerve Tissue of Diabetic Rats

目的观察中药筋脉通胶囊对链尿佐菌素(STZ)诱导的糖尿病大鼠周围神经组织内质网应激的影响。方法用STZ诱导建立DM大鼠模型,随机分为模型(DC)组、筋脉通小、中和大剂量组及硫辛酸(ALA)组,并设正常对照(NC)组。成模后即灌胃给药,筋脉通小、中、大剂量组分别按成人剂量的5、10和20倍给药,ALA组按成人剂量的10倍给药,持续16周。以免疫组化法检测背根神经节葡萄糖调节蛋白78(GRP78)及caspase-12蛋白表达,以q PCR检测坐骨神经GRP78及caspase-12的mRNA表达。结果与NC组相比,DC组的背根神经节GRP78和caspase-12的蛋白表达均升高(P<0.01)。与DC组相比,各治疗组背根神经节的GRP78和caspase-12的蛋白表达均下降(P<0.01)。与NC组相比,DC组坐骨神经的GRP78和caspase-12的mRNA的表达升高(P<0.01)。与DC组相比,各治疗组坐骨神经的GRP78和caspase-12的mRNA表达下降(P<0.01)。结论筋脉通胶囊可抑制糖尿病大鼠背根神经节及坐骨神经GRP78和caspase-12的表达,提示筋脉通胶囊改善糖尿病周围神经病变与其抑制内质网应激有关。

Objective To investigate the effects of Jinmaitong Capsule （.JMT） on endoplasmic reticulum stress in peripheral nerve tissue of streptozotocin （STZ） induced diabetic rats.Methods Diabetic rat models were induced by intra peritoneal injection of STZ,and were randomly divided into 5 groups including diabetic control group （DC）,low-dose JMT group （treated with JMT similar to the quintupling dose of adult recommended dosage）,middle-dose JMT group （treated with JMT similar to the decuple dose of adult recommended dosage）,high-dose JMT group （treated with JMT similar to the twenty-fold dose of adult recommended dosage） and α-Lipoic Acid group （ALA） （treated with ALA similar to the decuple dose of adult recommended dosage）.Eight normal rats matching with weight and age served as normal control group （NC）.All rats were given intragastric administration for 16 weeks and then culled.The expression of glucose-regulated protein 78 （grp78） and caspase-12 in dorsal root ganglia （DRG） was detected by immunohistochemical method; whereas the expression of mRNA of grp78 and caspase-12 in sciatic nerve was detected by real-time fluorogenetic quantitative PCR.Results Compared with NC,the expression of GRP78 and caspase-12 in DRG increased significantly in DC （P ＜ 0.01）.Compared with DC,the expression of GRP78 and caspase-12 in DRG decreased significantly in groups of ALA,low-dose JMT,middle-dose JMT and high-dose JMT （P ＜ 0.01）.Compared with NC,the expression of GRP78 and caspase-12 mRNA in sciatic nerve was increased significantly in DC （P ＜ 0.01）.Compared with DC,the expression of GRP78 and caspase-12 mRNA in sciatic nerve decreased significantly in groups of ALA,low-dose JMT,middle-dose JMT and high-dose JMT （P ＜ 0.01）.Conclusion Jinmaitong Capsule inhibits the expression of GRP78 and caspase-12 in DRG and sciatic nerve of diabetic rats.Its improvement of diabetic neuropathy might be partially related to its inhibition of endoplasmic reticulum stress.