Lipin1过表达对糖尿病大鼠周围神经病变的影响

Over expression of lipin1 attenuates diabetic peripheral neuropathy in rats

目的探讨脂素(Lipin1)对糖尿病(DM)大鼠周围神经早期病变的影响。方法应用高糖高脂饮食结合腹腔注射链脲佐菌素构建2型糖尿病(T2DM)动物模型,36只8周龄Wistar大鼠,随机分为空载体(LV-control)组、Lipin1过表达(LV-Lipin1)组,正常对照(NC)组。LV-Lipin1、LV-control组分别通过尾静脉注射Lipin1慢病毒载体与空慢病毒载体。8周后观察各组大鼠空腹血糖(FBG)、体质量(BW);测定坐骨神经传导速度(MNCV);观察坐骨神经病理形态学改变;应用免疫组化法测定Lipin1表达。结果 DM大鼠成模后8周时,LV-control组较NC组Lipin1表达减少,且神经纤维直径、密度、面积均减少(P<0.05);LV-Lipin1组神经纤维直径、密度、面积均较LV-control组改善(P<0.05);LV-Lipin1组较LV-control组坐骨神经神经传导速度明显改善(P<0.05)。结论DM周围神经病变大鼠坐骨神经中Lipin1表达降低,上调Lipin1表达后DM大鼠坐骨神经神经传导速度改善,病理学观察可见神经髓鞘结构和轴突形态的改善。

Objective To investigate the effects of lipinl on diabetic peripheral neuropathy in rats. Methods Type 2 diabetes meUitus was induced in male Wistar rats which were fed with high fatty and high sugar diet for 8 weeks, followed by streptozotocin （STZ） injection intraperitoneally. And then the models were randomly divided into Lipinl high expression （LV-Lipinl） group and empty vector （LV-control） group. Another 12 age-matched non-diabetic rats served as controls. Rats in LV-Lipinl group were transfected with lentiviral vector expressing rat lipinl ; rats in LV-control group were transfected with lentiviral empty vector. After two months, fasting blood glucose, body weight and the motor nerve conduction velocity （MNCV） were measured. Histopathological changes of sciatic nerve were analyzed with light microscope and electron microscope; Lipinl expression was evaluated with immunohistochemistry. Results Two months after diabetes was induced, expression of Lipinl in sciatic nerves was significantly decreased in the LV-control group compared with control group. The nerve fiber diameter, nerve fiber area and nerve fiber density in LV-control group were also decreased compared with control group. All of the above changes were significantly attenuated in LV-Lipinl group. Motor nerve conduction velocity （MNCV） of sciatic nerve in LV-Lipin-1 group was significantly improved compared with LV-control group （P 〈 0.05 ）. Conclusion Expression of Lipinl in sciatic nerve decreases in diabetic peripheral neuropathy rats. Upregulation of Lipinl expression significantly improves the MNCV and nerve pathological morphology.