论文标题:高血压大鼠靶器官病理改变、内皮功能、纤溶活性及药物干预研究
Experimental Study on Changes of Pathologic Ultrastructure Endothelia Function and the Activity of Fibrinoysis of Shr and Drugs Intervention
论文作者 刘同涛
论文导师 张运,论文学位 博士,论文专业 内科学
论文单位 山东大学,点击次数 155,论文页数 104页File Size21837k
2003-11-16论文网 http://www.lw23.com/lunwen_729597807/ 自发性高血压大鼠;内皮功能;纤溶活性;血管紧张素转换酶抑制剂;血管紧张素Ⅱ受体拮抗剂;钙拮抗剂;β受体阻滞剂
spontaneously hypertensive rats(SHR); The function of the endothelia cells; fibrinoysis; angiotensin-converting enzyme inhibitor;angiotensin receptor Ⅱ blockers; calcium antagonists; β -adrenoceptor antagonists
目的:本研究通过动物实验,研究自发性高血压大鼠(SHR)的血压、内皮功能、纤溶活性及靶器官病理结构的改变,并应用药物进行干预治疗,从而观察目前临床上常用的抗高血压药物及具有抗氧化作用的调脂药对SHR血压、内皮功能、纤溶活性的影响以及对靶器官的保护作用,为预防高血压心脑血管并发症的发生,指导临床用药,提供实验依据。 材料与方法:本研究采用的48只12周龄的雄性SHR,被随机分组为:厄贝沙坦(10mg/kg.d)治疗组8只;咪达普利(5mg/kg.d)治疗组8只;氨氯地平(5mg/kg.d)治疗组8只;普罗布考(10mg/kg.d)治疗组8只;卡维地洛(30mg/kg.d)治疗组8只;生理盐水(10ml/kg.d)对照组8只。同时另选同龄雄性正常血压对照大鼠(WKY组)8只,给予生理盐水10ml/kg.d。所有药物及生理盐水均采取人工灌胃,疗程8周。用大鼠尾压心率测定仪,测量各组大鼠用药前后的血压、心率;同时从大鼠静脉角处采血3ml,离心后收集血浆及血清,用硝酸还原酶法测定血清NO、NOS活性,用发色底物法测定血浆t-PA、PAI活性。于试验结束时,各组大鼠称重后腹腔内注射10%水合氯醛麻醉,开胸切取心脏,称左心室(含室间隔)和右心室湿重,计算左心室心脏重量指数(LVW/BW)和右心室心脏重量指数(RVW/BW),并取腹主动脉、心肌(左室游离壁)、脑组织和肾皮质,进行光学显微镜和电子显微镜观察脑组织、心肌、动脉血管壁及肾脏的病理结构。 结果:与WKY对照组相比,SHR组血压、心率、血浆PAI-1水平显著增高(P<0.01--0.001),血浆t-PA、血清NO、NOS水平显著降低(p<0.001)。
Objectives: To investigate changes of the blood pressure, the function of endothelium (NO, NOS), the activity of fibrinolysis, the microstructure and ultrastructure of the target organs in spontaneously hypertensive rats(SHR) by animal experiment; To observe the effect of antihypertensive drugs and anti-oxidation agents on the blood pressure ,the function of endothelium(NO, NOS),the activity of fibrinolysis and the protective function on the microstructure and ultrastructure of the target organs in SHR. To supply experimental evidences for prevention of complications of cerebrovascular and cardiovascular diseases, so to guide clinical drug administration.Material and Methods: Forty-eight 12-weeks old male SHRs were randomized into six groups (each group, n=8), who were fed respectively with irbesartan (10mg/kg.d), imidarpril(5mg/kg.d), amlodipine(5mg/kg.d), carvedilol (30mg/kg.d), probucol(10mg/kg.d), NS(10mg/kg.d) for 8 weeks. Eight age-matched male wistar-kyoto rats (WKY) were used as controls and fed with NS(10mg/kg.d) for 8 weeks. The blood pressure and the heart rate were measured by RBP-1 type rat tail-cuff monitor. Three milliliters of blood were collected at venous angle simultaneously. The plasma and the serum were collected after centrifugation. The technique of nitrate reductase was used to measure the activity of NO , NOS, and chromogenic substrate assay for t-PA and PAI-1. At the end of the experiment, each group of the rats were injected with 10% chloral hydrate into abdominal cavity after weighted. The left ventricule(including the ventricular septum ) and the right ventricule were weighted after thoracotomy. Then the left and right ventricular weight index (LVW/BW), (RVW/BW) were calculated. The microstructure and the ultrastructure of the brain, myocardium, blood vessel of artery, and the kidney were observed by light microscope and electron microscopy.Result:The values of blood pressure, heart rate, plasma PAI-1 were much greater in SHR groups than those in WKY group (P<0.01-0.001). But the levels of serum NO, NOS, plasma t-PA in SHR were significantly lower than those in WKY group(P<0.001). The levels of blood pressure were lowered after treatment in irbesartan imidaprih amlodipine> carvedilol groups except the probucol one(P<0.001). The change of heart rate was not significant after treatment in irbesartan > imidapril >amlodipine> and probucol groups(P>0.05), but the heart rate in carvedilol group were much lower than before(P<0.01). The levels of serum NO, NOS(P<0.001) and the activity of serum PAI-1 (P<0.001) were significantly decreased after being treated with irbesartan ? imidaprih amlodipine^ carvedilol and probucol. Level of plasma t-PA after treatment in irbesartan, imidapril and amlodipine groups were much higher than before. The level of plasma t-PA was not changed after treatment in probucol and carvedilol groups (P>0.05). The left ventricular weight, the left and right ventricular weight index of SHR were higher than those of WKY (PO.01). The left ventricular weight, the left and right ventricular weight index treated with irbesartan imidaprik amlodipine n carvedilol and probucol, especially the groups treated with irbesartan and imidapril were much lower than before.Under the transmission electron microscope , the myocardial cells of SHR control showed that: myocardial cells were hypertrophic, more myofilament were dissolved ,the arrangement of myocardial cells and myofibril were apparently turbulent, part Z thread disappeared; mitochondria assembly was hyperplastic, some mitochondria were swelling ^ some cavitated^ or ridgedisappeared; the shape of nucleolus was aberrant chromatin was sparse > the double deck structure of part kayotheca vanished. In the groups administrated with amlodipine> carvedilol and probucol, it appeared that the arrangement of myofibril was turbulent , mitochondria was swelling but the ridge was clear; nucleolus was lightly karyopyknotic, but the two-layer structure of kayotheca was clear; In the groups administered with irbesartan and imidarpril, it s
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