盐酸沙格雷酯改善糖尿病周围神经脱髓鞘病变的实验研究  

Experimental Study on Improving Effect of Shagrelate Hydrochloride on Demyelinating Lesion of Diabetic Peripheral Nerve

作　　者：董幼平[1] 陈凌[1] 李国徽 黄洁 DONG Youping;CHEN Ling;LI Guohui;HUANG Jie(Department of Endocrinology,the General Hospital of Ningxia Medical University,Yinchuan750004,China;Traditional Chinese Medicine Hospital of Yinchuan,Yinchuan750001,China;Department of Endocrinology,Hangang Hospital,Handan056001,China)

机构地区：[1]宁夏医科大学总医院内分泌科,银川750004 [2]宁夏银川市中医医院,银川750001 [3]邯钢医院内分泌科,邯郸056001

出　　处：《宁夏医科大学学报》2020年第11期1092-1097,共6页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金(NZ15276)。

摘　　要：目的探讨盐酸沙格雷酯对糖尿病周围神经脱髓鞘病变的作用。方法72只雄性SD大鼠,60只腹腔注射45 mg·kg^-1链脲佐菌素(STZ)诱发糖尿病模型,12只腹腔注射枸橼酸缓冲液作为对照组(NC,n=12)。将造模成功的46只糖尿病大鼠分为糖尿病组(DM,n=16只)、盐酸沙格雷酯治疗组(SHD,n=15只)、甲钴胺治疗组(MBN,n=15只)。SHD组大鼠给予盐酸沙格雷酯100 mg·(kg·d)^-1灌胃,MBN组给予甲钴胺135μg·(kg·d)^-1灌胃,给药12周。神经电生理方法检测坐骨神经感觉纤维的传导速度(SNCV)和动作电位振幅(SNAP);电镜观察坐骨神经组织脱髓鞘病变的改善情况;Western blot、免疫荧光法检测髓鞘蛋白MBP、P0的表达情况。结果与NC组比较,DM组、SHD组、MBN组大鼠体质量均降低,血糖增高(P均<0.01)。与NC组比较,DM组坐骨神经脱髓鞘病变严重,髓鞘蛋白表达水平降低,坐骨神经SNCV和SNAP均下降(P均<0.01)。与DM组相比,SHD组坐骨神经髓鞘病变明显减轻,SNCV和SNAP增高(P<0.01),免疫荧光及Western blot检测坐骨神经MBP和P0蛋白表达水平均有增高(P<0.01)。MBN组坐骨神经病变较DM组略有改善,SNCV和SNAP较DM组增高,但低于SHD组(P<0.05);MBN组MBP和PO蛋白表达均低于SHD组(P<0.01)。结论盐酸沙格雷酯对糖尿病周围神经髓鞘有保护作用,能延缓糖尿病大鼠周围神经脱髓鞘病变的发生、发展,从而改善神经功能。Objective To investigate the effect of sarpogrelate hydrochloride on peripheral nerve demyelination in diabetic rats.Methods A total of 72 male SD rats were included in this study,and 60 rats were intraperitoneally injected with STZ(45 mg·kg^-1)to induce diabetes model,12 rats were injected with citrate buffer as the control group.Forty six diabetic rats were divided into diabetic group(DM,n=16),sarpogrelate hydrochloride treatment group(SHD,n=15),and mecobalamin treatment group(MBN,n=15).SHD group rats were given 100 mg·(kg·d)^-1 hydrochloride by gavage,and MBN group rats were given 135μg·(kg·d)^-1 by gavage for 12 weeks.The nerve conduction velocity(SNCV)and action potential amplitude(SNAP)were measured by neuroelectrophysiological method.The improvement of demyelinating lesion was observed by electron microscopy.Western blot and immunofluorescence were used to detect the expression of MBP and P0.Results Compared with NC group,the body weight of DM group,SHD group and MBN group were significantly decreased(P all<0.01),and blood glucose was significantly increased(P all<0.01).Compared with the NC group the demyelinating lesion of sciatic nerve in DM group was serious,myelin protein expression level was significantly decreased,and sensory nerve SNCV and SNAP were significantly decreased(P<0.01).Compared with the DM group,the myelinopathy in the SHD group was significantly reduced,and SNCV and SNAP were significantly increased(P<0.01),MBP and P0 protein expression levels were significantly increased by immunofluorescence and Western blot(P<0.01).At 12 weeks,the pathological changes of sciatic nerve myelin sheath in MBN group were slightly improved than those in DM group,SNCV and SNAP were higher than those in DM group(P<0.05),but they were lower than those in SHD group(P<0.05).The myelin protein expression in MBN group was lower than SHD group(P<0.01).Conclusion Sarpogrelate hydrochloride had a protective effect on the myelin sheath of the peripheral nerve,which could delay the occurrence and development of

关 键 词：糖尿病周围神经病变 脱髓鞘 5-羟色胺 5-羟色胺2A受体阻滞剂 

分 类 号：R587.1[医药卫生—内分泌]