马钱苷减轻糖尿病视网膜病变大鼠视网膜病变的研究  

Research of loganin alleviates retinopathy in diabetic retinopathy rats

作　　者：徐林丽 闫萌萌 刘岩岩[2] 张艳[2] XU Lin-li;YAN Meng-meng;LIU Yan-yan;ZHANG Yan(Department of Surgical Teaching and Research,Higher VocationalSchool Cangzhou Medical College,Cangzhou 061000,Hebei Province,China;Department of Internal Medicine,Higher VocationalSchool Cangzhou Medical College,Cangzhou 061000,Hebei Province,China)

机构地区：[1]沧州医学高等专科学校外科教研室,河北沧州061000 [2]沧州医学高等专科学校内科教研室,河北沧州061000

出　　处：《中国临床药理学杂志》2025年第3期366-371,共6页The Chinese Journal of Clinical Pharmacology

基　　金：河北省沧州市重点研发指导基金资助项目(192106021)。

摘　　要：目的探讨马钱苷对糖尿病视网膜病变(DR)大鼠视网膜病变的影响与机制。方法通过注射链脲佐菌素及高糖高脂建立DR大鼠,并随机分为模型组(0.9%NaCl)、联合组[100 mg·kg^(-1)马钱苷+10 mg·kg^(-1)溶血磷脂酸(LPA)]和低、高剂量实验组(50 mg·kg^(-1)、100 mg·kg^(-1)马钱苷),另取10只正常大鼠为对照组(0.9%NaCl)。5组大鼠每天给药1次,连续6周。干预结束后,检测各组大鼠视网膜组织形态学、炎症因子和氧化应激水平、神经节细胞凋亡情况,以及视网膜组织中Ras同源基因家族成员A(RhoA)和Rho相关的卷曲螺旋激酶(ROCK)蛋白的表达水平。结果低、高剂量实验组和联合组、模型组、对照组的视网膜神经节细胞数分别为(19.75±1.90)、(24.32±2.15)、(17.80±1.94)、(15.44±1.65)和(28.30±2.02)个,白细胞介素-6水平分别为(85.67±8.61)、(68.88±6.91)、(98.52±9.88)、(108.24±10.83)和(62.08±6.22)ng·L^(-1),肿瘤坏死因子-α水平分别为(150.24±15.11)、(110.38±11.06)、(186.94±18.77)、(200.05±20.08)和(105.34±10.55)ng·L^(-1),丙二醛水平分别为(7.52±0.78)、(4.76±0.48)、(9.52±0.96)、(10.85±1.09)和(4.58±0.46)μmol·mg-1,超氧化物歧化酶活性分别为(62.05±6.21)、(78.22±7.83)、(52.11±5.23)、(50.21±5.04)和(79.61±7.98)U·mg^(-1),神经节细胞凋亡率分别为(12.71±1.06)%、(6.98±0.93)%、(14.69±1.30)%、(19.50±1.42)%和(2.15±0.38)%,RhoA蛋白相对表达水平分别为0.81±0.09、0.42±0.05、1.08±0.11、1.16±0.12和0.38±0.04,ROCK蛋白相对表达水平分别为1.28±0.13、0.77±0.08、1.72±0.18、1.85±0.19和0.63±0.07;对照组、高剂量实验组、联合组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论马钱苷可能通过抑制RhoA/ROCK途径的激活来抑制炎症和氧化应激反应,从而改善DR大鼠视网膜病变。Objective To investigate the effect and mechanism of loganin on retinopathy in diabetic retinopathy(DR)rats.Methods DR rats were established by injection of streptozotocin and high glucose and high fat.They were randomly grouped into model group(0.9%NaCl),experimental-L group,experimental-H group(50,100 mg·kg^(-1)loganin),combined group[100 mg·kg^(-1)loganin+10 mg·kg^(-1)lysophosphatidic acid(LPA)]and 10 normal rats were taken as control group(0.9%NaCl).After the intervention,retinal histomorphology,the levels of inflammatory factors and oxidative stress,apoptosis of ganglion cells,and the expression of Ras homologous gene family member A(RhoA)and Rho associated coiled coil-forming kinase(ROCK)proteins in retinal tissue were measured in turn.Results The number of retinal ganglion cells in experimental-L,-H groups,combined group,model group and control group were 19.75±1.90,24.32±2.15,17.80±1.94,15.44±1.65 and 28.30±2.02;the levels of interleukin-6 were(85.67±8.61),(68.88±6.91),(98.52±9.88),(108.24±10.83)and(62.08±6.22)ng·L^(-1);the levels of tumor necrosis factor-αwere(150.24±15.11),(110.38±11.06),(186.94±18.77),(200.05±20.08)and(105.34±10.55)ng·L^(-1);the levels of malondialdehyde were(7.52±0.78),(4.76±0.48),(9.52±0.96),(10.85±1.09)and(4.58±0.46)μmol·mg^(-1);the superoxide dismutase activities were(62.05±6.21),(78.22±7.83),(52.11±5.23),(50.21±5.04)and(79.61±7.98)U·g^(-1);the apoptosis rates of ganglion cells were(12.71±1.06)%,(6.98±0.93)%,(14.69±1.30)%,(19.50±1.42)%and(2.15±0.38)%;the relative expression levels of RhoA protein were 0.81±0.09,0.42±0.05,1.08±0.11,1.16±0.12 and 0.38±0.04;the relative expression levels of ROCK protein were 1.28±0.13,0.77±0.08,1.72±0.18,1.85±0.19 and 0.63±0.07,respectively.Compared with the model group,the above indexes of the control group,experimental-H group and combination group had statistical significance(all P<0.05).Conclusion Loganin may improve retinopathy in DR rats by inhibiting the activation of RhoA/ROCK pathway,inhibiting

关 键 词：马钱苷 糖尿病视网膜病变 Ras同源基因家族成员A Rho相关的卷曲螺旋激酶 氧化应激 炎症反应 

分 类 号：R28[医药卫生—中药学]