摘要
目的观察川芎嗪对早期糖尿病肾病(DN)大鼠足细胞nephrin、podocin表达及晚期糖基化终末化产物(AGEs)和P-选择素作用的影响,探讨其对DN大鼠的肾脏保护作用及其机制。方法采用高脂、高糖饮食联合链脲佐菌素(40 mg·kg^(-1),ip)建立糖尿病大鼠模型。糖尿病大鼠分为4组:模型组,二甲双胍组(250 mg·kg^(-1)),川芎嗪低剂量组(80 mg·kg^(-1))和高剂量组(160 mg·kg^(-1)),另取10只正常SD大鼠作为正常组,连续灌胃给药8 wk,正常组和模型组大鼠均灌胃给予等量蒸馏水。检测各组大鼠尿蛋白含量,取血测定血糖、肌酐(Cr)、内生肌酐清除率(Ccr)、尿素氮(BUN)、糖化血红蛋白(HbA_(1c))和AGEs、血管紧张素Ⅱ(AngⅡ)、P-选择素水平。观察各组大鼠肾脏病理学变化,Western blot方法检测肾组织nephrin、podocin蛋白表达水平。结果治疗8 wk后,与正常组比较,模型组大鼠尿蛋白、血糖、BUN、Cr、AngⅡ、P-选择素、HbA_(1c)、AGEs水平均明显升高(P<0.01),Ccr、肾脏nephrin和podocin蛋白表达下降(P<0.01)。二甲双胍组和川芎嗪高剂量组大鼠BUN、Cr低于模型组(P<0.05),二甲双胍组和川芎嗪高、低剂量组大鼠血糖、AngⅡ、P-选择素、HbA_(1c)、AGEs水平低于模型组(P<0.05),肾组织nephrin和podocin蛋白表达高于模型组(P<0.01),且肾脏组织病理性损伤明显减轻。结论川芎嗪对早期DN大鼠肾脏具有保护作用,其机制可能与诱导nephrin、podocin表达增加及抑制AGEs和P-选择素水平有关。
AIM To investigate the effects of ligustrazine on the advanced glycation end products (AGEs),P-selectin,podocyte nephrin and podocin in rats with early diabetic nephropathy,and explore its protective effects for kidney and possible mechanisms.METHODS The model of diabetic rat was established by integrated method of high lipid,sugar diets and streptozotocin(40 mg?kg^(-1),ip).The diabetic rats were divided into 4 groups;model,metformin(250 mg?kg^(-1)) and ligustrazine low dose(80 mg?kg^(-1)),ligustrazine high dose(160 mg?kg^(-1)) groups.In addition,10 normal SD rats were used as control group.Each group was given drugs and equals distilled water by gavage for 8 weeks.At the end of experiment,the levels of fasting blood glucose(FBG),creatinine(Cr),creatinine clearance(Ccr),blood urea nitrogen(BUN),glycosylated hemoglobin A1(HbA_(1c)),AGEs,angiotensinⅡ(AngⅡ) and P-selectin in serum and urinary protein were measured.The pathological changes of the kidney were observed under optic microscope.Expressions of nephrin and podocin in kidney were determined by Western blot analysis.RESULTS Compared with those in the control group,the levels of FBG,Cr,BUN,HbA_(1c),AGEs,AngⅡ,P-selectin and urinary protein were significantly increased in the model group(P < 0.01),while Ccr,protein expressions of nephrin and podocin were decreased(P < 0.01).The levels of BUN and Cr in the metformin group and the ligustrazine high dose group were lower than those in the model group(P < 0.05).The levels of FBG,HbA_(1c),AGEs,AngⅡand P - selectin in the metformin group and the ligustrazine group were lower than those in the model group(P < 0.05),while protein expressions of nephrin and podocin were higher(P < 0.01) and glomerular pathological changes were improved significantly.CONCLUSION Ligustrazine can protect kidney in rats with early diabetic nephropathy,and its mechanisms may be related to up - regulating protein expressions of nephrin and podocin and inhibiting of AGEs and P-selectin.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2012年第10期618-623,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
广东省科技计划项目(2009B060700020)
