机构地区:[1]安徽中医药大学药学院/现代中药安徽省工程技术研究中心,安徽合肥230031 [2]安徽中医药大学第一附属医院检验科,安徽合肥230031
出 处:《中药材》2013年第6期953-958,共6页Journal of Chinese Medicinal Materials
基 金:国家自然科学基金(81102682);安徽省高等学校优秀人才基金(2011SQRL091)
摘 要:目的:观察益气活血药对黄芪丹参对糖尿病肾病模型大鼠尿蛋白、肾功能、肾小管重吸收的影响,并探讨其机制。方法:采用链脲佐菌素单次大剂量(55mg/kg)腹腔注射,诱导大鼠糖尿病肾病(DN),造模成功后随机分成模型组、益气活血组(黄芪和丹参注射液给药组)、格列喹酮组,同时设置正常对照组。于给药第6周尾静脉注射FITC-BSA,取各组大鼠的尿液检测24h尿蛋白量,血液测定血糖、血清尿素氮、血清肌酐、血清甘油三酯及血清总胆固醇;取肾脏制成组织匀浆测定LPO、SOD、GSH-Px和高级糖基化终产物(AGEs),肾脏石蜡切片用于PAS、HE及免疫组化染色。结果:与正常对照组比较,模型组大鼠体质量显著降低,血糖、24h尿蛋白量、血清肌酐、血清尿素氮、血清甘油三酯、血清总胆固醇均显著增加,肾组织中LPO和AGEs的含量显著增加(P<0.01),GSH-Px和SOD的活性显著下降(P<0.05)。益气活血药对可显著降低DN大鼠24h尿蛋白量(P<0.01),显著降低血清肌酐、血清尿素氮,血清甘油三酯和血清总胆固醇的水平(P<0.05),并可以降低DN大鼠肾组织中LPO和AGEs的含量(P<0.05),升高GSH-Px的活性(P<0.05)。肾脏切片染色结果显示益气活血药对可显著改善糖尿病肾脏肾小管的病变,并提高肾小管对FITC-BSA的重吸收能力。免疫组化结果表明黄芪丹参合用可以增加肾小管上皮细胞megalin表达。结论:益气活血法治疗可以改善糖尿病肾病大鼠肾小管的病变,减少蛋白尿,改善肾小管重吸收功能,其机制可能与增加肾脏组织的抗氧化活性,增加肾小管上皮细胞megalin表达有关。Objective:To investigate the effect of Chinese herbal medicine with Supplement Qi and Activating Blood Circulation ( huangqi and danshen) on urinary protein, kidney function and tubular reabsorption of diabetic nephropathy rats. Methods:SD rats were randomly divided into a nondiabetic control group (normal group) and three groups in which diabetes were induced by a single intraperitoneal injeetion of freshly prepared streptozotocin( STZ ,55 mg/kg body weight). Then the di/ibetes rats were randomly assigned to three groups :diabetic model group ,Supplement Qi and Activating Blood Circulation traditional Chinese medicine group( huangqi and ! danshen group) and Gliquidone group (as a reference hypoglyeemie drug). Each group was treated with corresponding drugs for 6 weeks. At the end of the study,the rats from each group were injected with FlTC-labeled BSA through tail vein. The 24 h urinary protein excretion were measured anti blood was collected for measuring plasma glucose levels, serum ereatinine (Cr), blood urea nitrogen (BUN) , triglyeeride(TG) and total cholesterol(T-CHO). Renal tissue was used to measure the level of LPO ,SOD, GSH-Px and AGEs and Paraffin-embedded sections were stained with HE, PAS and immunohistochemistry. Results:The plasma glucose, the 24 h urinary protein excretion,the levels of serum Cr, B UN,TG and T-CHO in STZ-induced diabetic rats were higher than those of nondiabetic rats. Diabetic rats showed significantly increase in LPO and AGEs ( P 〈 0. 01 ) and decrease in antioxidant enzyme activity ( both GSH-Px and SOD ) ( P 〈 0. 05 ) as compared with non-diabetic control rats. Treatment with the Supplement Qi and Activating Blood Circulation traditional Chinese medicine for 6 weeks in diabetic rats significantly reduced the 24 h urinary protein excretion compared with model control (P 〈0. 01 ) ,and markedly decreased the levels of serum Cr,BUN,TG and T-CHO as compared with those of diabetic rat(P 〈 0. 05). The levels o
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