摘要
目的观察枸杞多糖对糖尿病周围神经病变(DPN)大鼠的保护作用,并通过PERK-CHOP信号通路探讨其作用机制。方法采用高脂高糖饲料+链脲佐菌素(STZ)腹腔注射法制备DPN大鼠模型,分别设立空白组、模型组、α-硫辛酸组、枸杞多糖低剂量、高剂量组,观察枸杞多糖对大鼠血糖、体质量的影响,HE染色观察大鼠坐骨神经病理学变化,透射电镜观察大鼠坐骨神经超微结构改变,Western-blot检测坐骨神经GRP78、PERK、p-PERK、CHOP及Bax、Bcl-2的蛋白表达,RT-PCR检测GRP78、PERK、CHOP的mRNA表达。结果经枸杞多糖低、高剂量组治疗后,血糖水平较模型组显著降低,体质量明显增高(P<0.05),大鼠坐骨神经病理损伤得到有效减轻,下调了坐骨神经中Bax及PERK-CHOP通路的蛋白和mRNA表达,同时上调了Bcl-2表达和Bcl-2/Bax比值(P<0.05)。结论枸杞多糖能够有效改善DPN大鼠血糖水平,减轻大鼠坐骨神经损伤,可能通过抑制PERK-CHOP通路激活所致的内质网应激(ERS)和细胞凋亡发挥作用,高剂量对多项指标的改善较低剂量更为明显。
Objective To observe the protective effects of Lyciumbarbarum polysaccharides(LBP)on diabetic peripheral neuropathy(DPN)in rats and explore its mechanism through PERK-CHOP signaling pathway.Methods The rat model of DPN was prepared by intraperitoneal injection of high fat and high sugar diet and streptozotocin(STZ).This study was randomly divided into blank group,model group,α-Lipoic acid group,LBP low-dose group and LBP high-dose group.The effects of Lyciumbarbarum polysaccharides on blood glucose and body mass of rats were determined.The changes of sciatic neuropathy were observed by HE staining.The ultrastructural changes of sciatic nerve and myelin sheath were observed by transmission electron microscope.The protein and mRNA expression levels of GRP78,PERK,phosphorylated-PERK(p-PERK),CHOP,Bax and Bcl-2 in sciatic nerve were detected by Western blot and RT-PCR assays.Results Compared with the model group,the blood glucose level and body weight in LBP low-dose and high-dose groups were significantly decreased.The pathological injury of sciatic nerve was effectively alleviated.The protein and mRNA expressions of Bax and PERK-CHOP pathway in sciatic nerve were down-regulated,and the expression of Bcl-2 and the ratio of Bcl-2/Bax were decreased.Conclusion Lyciumbarbarum polysaccharide couldimprove the blood glucose level of DPN rats and alleviate the injury of sciatic nerve and its mechanism might be related to the inhibition of endoplasmic reticulum stress(ERS)and apoptosis induced by PERK-CHOP pathway activation.
作者
吴秀丽
徐琴
胡爽
刘相
谌芬
彭亚军
Wu Xiuli;Xu Qin;Hu Shuang;Liu Xiang;Shen Fen;Peng Yajun(Department of Nephrology,the First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Huna 410007,China)
出处
《遵义医科大学学报》
2023年第5期459-465,共7页
Journal of Zunyi Medical University
基金
湖南省中医药科研计划项目(NO:2021027)。
