摘要
目的探讨降糖饮对糖尿病性周围神经病变(DPN)大鼠血清NGF、BDNF、TGF-β1和脂代谢的影响。方法采用链脲佐菌霉素制备DPN模型并随机分为DPN模型组、降糖饮低(5 g/kg)、中(10 g/kg)和高剂量(20 g/kg)组、阳性药组(依帕司他片20 mg/kg),健康大鼠为正常组,每组15只大鼠。各给药组灌胃给药,DPN模型组及正常组灌胃给予生理盐水,所有组别连续灌胃3个月。记录所有组别大鼠的生存状态、体质量及空腹血糖(FBG)的变化,ELISA法检测血清NGF、BDNF、TGF-β1、全自动生化仪检测TC、TG、FFA、LDL,免疫印迹法检测脂质分解代谢相关蛋白[肉碱棕榈酰转移酶(CPT-1)、过氧化物酶体增殖物激活受体α(PPAR-α)、固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)和二酰甘油-O-酰基转移酶同源物2(DGAT2)],苏木精-伊红(HE)染色检测脑病变。结果正常组大鼠毛发光滑,DPN模型组萎缩畏寒,体质量增加缓慢,低、中、高剂量降糖饮组及阳性药组的活动量略有减少,生存状态介于正常组和DPN模型组之间。各组大鼠入组时的体质量及FBG差异无统计学意义(P>0.05)。治疗前,与正常组比,DPN模型组、降糖饮低、中、高剂量组及阳性药组的体质量明显降低(P<0.05),FBG明显增高(P<0.05),治疗后,与DPN模型组比,降糖饮低、中、高剂量组及阳性药组体质量明显增高(P<0.05),FBG明显降低(P<0.05),且呈降糖饮剂量依赖性趋势。与正常组比,DPN模型组血清NGF和BDNF明显降低(P<0.05),TGF-β1明显增高(P<0.05),与DPN模型组比,降糖饮低、中、高剂量组及阳性药组血清NGF和BDNF明显增高(P<0.05),TGF-β1明显降低(P<0.05),且呈降糖饮剂量依赖性趋势。与正常组比,DPN模型组外周血TC、TG、FFA和LDL均明显增高(P<0.05),与DPN模型组比,降糖饮低、中、高剂量组及阳性药组TC、TG、FFA和LDL均有不同程度地降低(P<0.05),且呈降糖饮剂量依赖性趋势。与正常组比,DPN模型组外周血CPT-1、PPAR-α均明显降低(P<0.05),SREBP-1c、FAS和DGAT-2均明显增高,与DPN模型组比,降糖饮低、中、高剂量组及阳性药组外周血CPT-1、PPAR-α均明显增高(P<0.05),SREBP-1c、FAS和DGAT-2均明显降低,且呈降糖饮剂量依赖性趋势。正常组坐骨神经纤维结构紧密,分布整齐,DPN模型组大鼠坐骨神经纤维疏松,多处断裂或变性,存在大量炎性病灶,降糖饮低、中、高剂量组及阳性药组的坐骨神经断裂或变性明显减少,局部存在炎性反应,病理改善程度呈降糖饮剂量依赖性趋势。结论降糖饮治疗DPN的可能机制在于增高血清NGF、BDNF,降低TGF-β1,改善脂代谢。
Objective To investigate the effect of Jiangtangyin on serum NGF,BDNF,TGF-β1 and lipid metabolism of diabetic peripheral neuropathy(DPN)rats.Methods The DPN rats was prepared by streptozotocin and randomly divided into 5 groups:the DPN model group,Jiangtangyin low(5 g/kg),medium(10 g/kg)and high dose(20 g/kg)groups and the positive drug(pastata tablets(20 mg/kg)group.The healthy rats as the normal group,15 rats in each group.3 Jiangtangyin groups and the positive drug group were administered by intragastric administration,respectively.The DPN model group and the normal group were intragastrically saline solution.And all groups were continuously intragastrically administered for 3 months.The survival status,body weight and fasting blood glucose(FBG)during the treatment were recorded.After treatment,the rats were sacrificed.The TC,TG,FFA,LDL,immunoblot detection of lipid catabolism related proteins(CPT-1,PPAR-α,SREBP-1c,FAS DGAT2).HE staining to detect brain lesions.Results The rats in the normal group were fed and drinking normally,and their hair was shiny and smooth.The DPN model group was atrophied and chilled.The intake and drinking water increased and the body weight increased slowly.The activity of Jiangtangyin low,medium and high dose groups and the positive drug group decreased slightly.The survival status was between the normal group and the DPN model group.There was no statistically significant difference in body weight and FBG within groups when entering our study(P>0.05).Before treatment after DPN was prepared,compared with the normal group,the body weight of the DPN model group,Jiangtangyin low,medium,high dose group and positive drug group significantly decreased(P<0.05),FBG significantly increased(P<0.05).After treatment,compared with DPN model group,the body weight of the Jiangtangyin low,medium,high dose group and positive drug group significantly increased(P<0.05),FBG significantly decreased(P<0.05),and showed a dose-dependent trend of Jiangtangyin.Compared with the normal group,serum NGF and BDNF in the DPN model group significantly reduced(P<0.05),and TGF-β1 significantly increased(P<0.05).Compared with the DPN model group,Jiangtangyin low,the serum NGF and BDNF in the Jiangtangyin medium and high dose groups and positive drugs increased significantly(P<0.05),TGF-β1 decreased significantly(P<0.05),and showed a dose-dependent trend of Jiangtangyin.Compared with the normal group,the peripheral blood TC,TG,FFA and LDL of the DPN model group significantly increased(P<0.05).Compared with the DPN model group,TC,TG,TC,TG,FFA and LDL decreased(P<0.05),and showed a dose-dependent trend of Jiangtangyin.Compared with the normal group,CPT-1 and PPAR-αin the peripheral blood of the DPN model group significantly reduced(P<0.05),SREBP-1c,FAS and DGAT-2 significantly increased(P<0.05).Compared with the DPN model group,the CPT-1 and PPAR-αin the peripheral blood of the Jiangtangyin lower,middle and high dose groups and the positive drug group significantly increased(P<0.05),SREBP-1c FAS and DGAT-2 significantly reduced(P<0.05),showed a dose-dependent trend of Jiangtangyin.The sciatic nerve fibers in the normal group were tightly packed and neatly distributed.The sciatic nerve fibers of the DPN model group were loose,with multiple fractures or degeneration,and there were a large number of inflammatory lesions.The sciatic nerve fibers in Jiangtangyin lower,middle and high dose groups and the positive drug group had less fractures or degeneration,with local inflammatory reaction,pathological improvement showed a dose-dependent trend of Jiangtangyin.Conclusion The possible mechanism of Jiangtangyin in treating DPN is to increase serum NGF and BDNF,reduce TGF-β1,and improve lipid metabolism.
作者
孙磊
王超君
SUN Lei;WANG Chao⁃jun(Emergency department of 901 Hospital of the people′s Liberation Army,Hefei 230032,China)
出处
《解剖学研究》
CAS
2020年第5期428-434,共7页
Anatomy Research
