氧化应激促进凋亡相关因子在糖尿病大鼠坐骨神经中表达的研究

Study on oxidative stress promoting the expression of apoptosis-associated factors in sciatic nerve of diabetic rat

目的观察糖尿病早期大鼠坐骨神经组织中氧化应激损伤和凋亡相关因子表达情况及其相关性,进一步探讨糖尿病周围神经病变(DPN)的发病机制。方法采用链脲佐菌素(STZ)一次性腹腔注射诱导糖尿病大鼠模型。随机选取成模大鼠17只作为模型组(M组),另设正常对照组(N组)大鼠15只。8周后,取大鼠左侧坐骨神经,采用HE染色观察形态学改变,并采用免疫组化法检测8-羟基脱氧鸟苷(8-OHdG)和Caspase-3表达,Western blot分析检测发动相关蛋白-1(Drp-1)和Bax的表达。结果与N组相比,M组大鼠坐骨神经形态学改变明显,体重增加不明显,血糖明显增高,差异有统计学意义(P<0.05);Drp-1、Bax、8-OHdG及Caspase-3表达均增多,差异有统计学意义(P<0.05)。M组8-OHdG与Caspase-3表达呈明显正相关(r=0.798,P<0.05)。结论早期糖尿病大鼠坐骨神经组织中氧化应激损伤促进凋亡相关因子表达增多,最终促发细胞凋亡可能是DPN发病原因之一。

Objective To investigate oxidative stress injury with the expression and correlativity of apoptosis-associated factors in sciatic nerve of diabetic rat in early stage,and further discuss the pathogenesis of diabetic peripheral neuropathy（DPN）.Methods A single intra-peritoneal injection of streptozotocin（STZ） was used to induce diabetic rats models,and 17 diabetic rats were picked up randomly as diabetic group（M group）.Normal control group（N group）was set up too.8 weeks later,left sciatic nerves were dissected,and morphological alteration was valued by HE staining.The expression of 8-hydroxy-2-deoxyguanosine（8-OHdG） and Caspase-3 in sciatic nerve tissue was detected by immunohistochemistry,and the expression of dynamin-related protein l（Drp-1） and Bax was detected by western blot.Results Compared with N group,sciatic nerve tissues in M group showed obvious morphological alteration,the body weight of rats did not increase significantly,but blood glucose levels raised significantly（P0.05）,and the expression of protein Drp-1,Bax,8-OHdG and Caspase-3 also increased significantly（P0.05）.In M group,the expression of 8-OHdG showed a positive correlation with Caspase-3（r=0.798,P0.05）.Conclusion Oxidative stress in sciatic nerve of early diabetic rats induces overexpression of apoptosis-associated factors,and finally promotes apoptosis may play an important role in contributing DPN.