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川芎嗪联合贝纳普利防治GK大鼠并发肾病的实验研究及机理探讨
【作者】 彭涛；
【导师】 谢春光；
【作者基本信息】 成都中医药大学 ， 中医内科学， 2008， 博士
【摘要】 目的:初步观察川芎嗪联合贝那普利对GK大鼠并发肾病的大鼠肾组织TNF-α、ICAM-1、OPN等表达水平的防治作用并探讨其调控作用的可能机制;探讨DN病变程度与炎症表达的关系,并进一步探讨糖尿病肾病的发病机制,寻找早期诊断及评价DN病变的新指标。方法:将40只雄性GK大鼠随机分为模型组、贝那普利组、川芎嗪组、川芎嗪+贝那普利组;每组10只。模型组,按5ml·kg-1·d-1灌服生理盐水;贝那普利组,按1.6mg·kg-1·d-1灌服贝那普利悬液;川芎嗪组,按150mg·kg-1·d-1灌胃（其浓度为20mg/ml）;川芎嗪+贝那普利组,川芎嗪按150mg·kg-1·d-1灌服,加灌贝那普利悬液(按1.6mg·kg-1·d-1);共16周。实验第8周、第12周和第16周将大鼠放入代谢笼中,收集24h尿液,测定24h尿蛋白定量;治疗16周后,将大鼠用3%戊巴比妥钠腹腔麻醉后剖腹,摘取肾脏。反转录聚合酶链反应法（RT-PCR）测肾组织TNF-α、OPN含量,免疫组化检测肾脏ICAM-1的表达,并测定各组大鼠血IL-6和尿RBP水平。结果:与其它组比较,模型组大鼠血糖明显增高（P＜0.05）,24h尿蛋白定量明显升高（P＜0.05）,肾组织TNF-α、ICAM-1、OPN表达明显增加（P＜0.05,或p＜0.01）;血IL-6和尿RBP、24h尿蛋白等指标增加（P＜0.05,或p＜0.01）。川芎嗪联合贝那普利能降低血糖、TG和TC;下调肾组织TNF-α、ICAM-1、OPN表达水平,降低血清肌酐、尿素氮水平,提高内生肌酐清除率,减少尿白蛋白的排泄,降低IL-6水平;从而改善DN大鼠的肾功能。结论:川芎嗪联合贝那普利能降低糖尿病肾病大鼠血糖水平,改善DN大鼠肾功能,改善肾组织炎症病变和抗凝作用。下调肾组织TNF-α、ICAM-1、OPN表达和降低IL-6水平可能为其作用机制之一。
【Abstract】 Objective:To observe ligustrazine combined with benazepil tablets prevention and cure in expression level of intercellular adhesion molecule-1（ICAM-1）、tumour necrosis factor-α（TNF-α） and osteopontin （OPN） in GK rats nephridial tissue tentatively and evalute the possible mechanisms of effects on diabetic neuropathy（DN） on earlier period. To probe into the connection between diabetic neuropathy and inflammatory to open out the possible mechanisms of DN for appraising and diagnosing new quideline on diabetic neuropathy on earlier period.Methods:Forty GK male rats were randomly divided into four groups: 10 every groups,respectively for model group,ligustrazine group, benazepil group and ligustrazine combined with benazepil group.Drench with NS 5ml·kg-1·d-1、benazepill.6mg·kg-1·d-1、ligustrazine 150mg·kg-1·d-1、ligustrazine combined with benazepil(150mg·kg-1·d-1+1.6mg·kg-1·d-1) to rats respectively,according to the group in 16 weeks.Puting big mouses into metabolism cages in the 8th week,the 12th week and the16th week,collecting urine to determine quantitation of Urine protein in 24 hours.Treat for 16 weeks,anaesthetize the big mouse by 3% pentobarbital,then cut open the belly of rats and pick its kidney, examine TNF-αand OPN content in renal organize by means of RT-PCR and ICAM-1 content by means of immunohistochemistry,and determine IL-6 level in blood serum and RBP level in emiction of every group.Result:Compared with other group,the blood glucose of model group rats increase obviously（P＜0.05）,quantitation of 24h Urine protein rise obviously（P＜0.05）,degrade the express level of TNF-α、ICAM-1 and OPN in renal organizes increase obviously（P＜0.05,或p＜0.01）;blood Indexes such as IL-6 and RBP level in emiction are improved（P＜0.05,或p＜0.01）. ligustrazine combined with benazepil tablets can protect the kidney for lowerring blood glucose、TG and TC、degrading TNF-α、ICAM-1 and OPN express level in renal organize,decreasing serum albumin、blaood urea mitrogen and increasing creatinine clearance,at the same time,reducing Urine protein and IL-6 levelConclusion:ligustrazine combined with benazepil can reduce great mouse blood glucose level of diabetic rats and improve nephric tubule pathological change,moreover;it can play its roles depend on resisting inflammation and anticoagulatory function.One of the possible mechanisms of DN is to degrade TNF-α、ICAM-1 and OPN express level in renal organize and reduce IL-6 level in blood serum.