中西药联合降脂治疗肾动脉粥样硬化性高血压的研究

发布时间：2019-07-01 12:18

【摘要】：第一部分临床分析研究目的:回顾性分析肾动脉粥样硬化性狭窄(Atherosclerotic renal artery stenosis,ARAS)患者的发病情况,分析并识别ARAS的高危因素,以助于ARAS的早期发现、早期干预。研究方法:选取就诊于吉林大学第二医院行肾动脉造影或肾动脉CTA,病例资料完整,符合纳入标准的住院患者共245例。对患者的年龄、性别、血脂、肾功能等情况以及是否合并冠心病、高血压、糖尿病、脑梗塞等疾病进行回顾性分析。研究结果:与195例非肾动脉狭窄患者相比,50例肾动脉狭窄患者在合并高龄、高血压病史、脑梗塞病史、冠脉双支病变、三支病变或左主干病变、吸烟史、血脂异常及肾功能不全的人数比例明显增多,具有显著差异(P0.05)。对上述因素行Logistic回归分析显示,年龄(㧐60岁)、高血压病史、冠脉三支病变、左主干病变、吸烟史、血脂异常、肾功能不全等是ARAS的危险因素。研究结论:年龄(㧐60岁)、高血压病史、冠脉三支病变、左主干病变、吸烟史、血脂异常、肾功能不全是预测ARAS的独立危险因素,对合并有上述危险因素的患者应高度警惕是否患有ARAS。第二部分实验研究研究目的:通过建立肾动脉粥样硬化性高血压大鼠模型,观察并对比不同降脂方案的疗效和副作用,探讨更好的ARAS的治疗方案。研究方法:1、建立动物模型,采用平行针灸针缩窄法建立大鼠肾动脉狭窄模型,假手术组(F组)只暴露肾动脉,不予狭窄;将手术组中大鼠分为普通饲料喂养组(N组)和高脂饲料喂养组(T组),8周后T组大鼠建立ARAS性高血压模型。2、根据不同降脂方案干预模型大鼠,将T组大鼠随机分为5组:生理盐水组(T0组)、血脂康组(T1组)、常规剂量瑞舒伐他汀组(T2组)、常规剂量瑞舒伐他汀联合血脂康组(T3组)、小剂量瑞舒伐他汀联合血脂康组(T4组)。药物干预6周后,检测并对比用药前后各组血压、血脂(TC、TG、HDL-C、LDL-C)、肝功(ALT、AST)、肾功(BUN、Scr)、动脉粥样硬化相关因子(NO、ET-1、MPO、MMP-9)的变化及主动脉、肾脏、肝脏的病理改变。研究结果:1、与假手术组(F组)相比,手术组血压可见明显升高,BUN、Scr升高显著(P0.05),成功建立肾动脉狭窄性高血压模型。手术组中,与普通喂养组(N组)相比,高脂喂养组(T组)TC、TG、LDL-C显著升高,HDL-C显著降低(P0.05);动脉粥样硬化相关因子NO下降、ET-1、MPO、MMP-9升高(P0.05);ALT、AST未见明显改变;病理结果显示,T组主动脉可见动脉粥样硬化性改变,肾脏可见肾小管萎缩及不同程度的变性,肝脏脂肪空泡堆积明显,成功建立ARAS性高血压大鼠模型。2、药物干预6周后,与用药前相比,各用药组血压可见略有下降,差异未见统计学意义(P0.05);各用药组均可见TC、TG、LDL-C降低,HDL-C升高,(P0.05),其中T3、T4两组血脂改善最为明显,T3组略优于T4组,但两组组间未见明显差异(P0.05);T2、T3组ALT、AST显著升高(P0.05),而T1、T4组未见明显改变(P0.05);各用药组BUN、Scr水平均较用药前降低(P0.05),其中T3、T4组下降最明显,T3略优于T4组,但两组组间未见显著差异(P0.05);T3、T4组均可见动脉粥样硬化相关因子NO明显升高,ET-1、MPO、MMP-9显著降低(P0.05),T3组改善最明显,T4组与T3组组间未见显著差异。与T0组相比,各用药组主动脉粥样硬化病变、肾脏肾小管变性程度均可见不同程度的减轻,肝脏脂肪空泡明显减少,其中T3、T4组改善最明显,T3组略优于T4组,但两组差异不大,此外,T2、T3组部分大鼠肝脏可见肝细胞坏死,炎细胞浸润严重。研究结论:1、小剂量瑞舒伐他汀联合血脂康治疗ARAS性高血压模型大鼠可达到理想降脂效果的同时,对肾脏具有保护作用,且对肝功能的损害作用小。2、小剂量瑞舒伐他汀联合血脂康可有效调节动脉粥样硬化相关因子,控制炎症反应,保护内皮细胞,抑制ARAS的发生发展。
[Abstract]:Objective: To analyze and identify the risk factors of ARAS in patients with ARAS in order to help the early detection and early intervention of ARAS. Methods: The renal artery angiography or the renal artery CTA in the second hospital of Jilin University was selected and the case information was complete. The age, sex, blood lipid and renal function of the patient and the combination of coronary heart disease, hypertension, diabetes, and cerebral infarction were analyzed retrospectively. Results: Compared with 195 patients with non-renal artery stenosis,50 patients with renal artery stenosis had a significant increase in the proportion of the elderly, the history of hypertension, the history of cerebral infarction, the double-branch of the coronary artery, the three-vessel or the left main lesion, the history of smoking, the abnormal blood lipid and the renal insufficiency. There was a significant difference (P0.05). Logistic regression analysis of the above factors showed that age (? The risk factors of ARAS were the history of hypertension, the three cases of coronary artery, the left main lesion, smoking history, dyslipidemia, and renal insufficiency. Study Conclusion: Age (? 60-year-old), history of hypertension, three-vessel coronary artery disease, left main lesion, smoking history, dyslipidemia, renal function were not all the independent risk factors for predicting the ARAS, and the patients with the above risk factors should be highly alert for ARAS. In the second part, the aim of the study was to observe and compare the efficacy and side effects of different lipid-reducing regimens by establishing a model of the atherosclerotic hypertension rats, and to discuss the treatment plan of the better ARAS. Methods:1. The model of the renal artery stenosis was established by using the parallel acupuncture and the narrow method, and the renal artery was only exposed in the sham operation group (group F). The rats in the operation group were divided into the common feed group (N group) and the high-fat feed group (T group). The rats of T group were randomly divided into 5 groups: normal saline group (T0 group), Xuezhikang group (T1 group) and routine dose of rosuvastatin group (T2 group). The routine dose of rosuvastatin combined with the Xuezhikang group (T3 group), the low dose of the rosuvastatin and the Xuezhikang group (group T4). The changes of blood pressure, blood lipid (TC, TG, HDL-C, LDL-C), liver function (ALT, AST), renal function (BUN, Scr), atherosclerosis-related factors (NO, ET-1, MPO, MMP-9) and the pathological changes of the aorta, the kidney and the liver were detected and compared after 6 weeks of drug intervention. Results:1. Compared with the sham operation group (F group), the blood pressure of the operation group was significantly higher than that of the sham operation group (group F), and the BUN and Scr increased significantly (P0.05), and the renal artery stenosis hypertension model was successfully established. In the operation group, the TC, TG, LDL-C of the high-fat-fed group (T-group) were significantly higher than that of the normal-feeding group (group N), and the HDL-C decreased significantly (P0.05); the NO of the related factors of atherosclerosis, ET-1, MPO and MMP-9 increased (P0.05); the ALT and AST did not change significantly; the pathological results showed that, In that t group, the atherosclerotic changes of the aorta, the renal tubular atrophy and the degree of degeneration in the kidney, the accumulation of fat vacuoles in the liver, and the successful establishment of the ARAS hypertensive rat model.2. After 6 weeks of drug intervention, the blood pressure of each group decreased slightly after 6 weeks of drug intervention. The levels of TC, TG, LDL-C decreased and HDL-C was higher in all treatment groups (P0.05). There was no significant difference between the two groups (P0.05), but there was no significant difference between the two groups (P0.05), and the levels of ALT and AST in the T2 and T3 groups were significantly higher (P0.05). The levels of BUN and Scr in the treatment group were lower than that of T4 (P0.05), but there was no significant difference between the two groups (P0.05). There was no significant difference in the level of ET-1, MPO and MMP-9 in the group of T4 (P0.05). Compared with the T0 group, the degree of renal tubular degeneration and the degree of renal tubular degeneration of each treatment group were relieved, and the fat vacuoles of the liver were significantly reduced, in which the improvement of T3 and T4 group was the most obvious, and the T3 group was slightly better than that of the T4 group, but the difference between the two groups was not small, and, in addition, T2, In the T3 group, the liver of the rat liver was found to be necrotic and the inflammatory cells had a serious infiltration. The results of the study:1. The combination of low dose of rosuvastatin and Xuezhikang in the treatment of ARAS high blood pressure model rats can achieve the ideal lipid-lowering effect, has a protective effect on the kidney, and has little effect on the liver function. The combination of low-dose rosuvastatin and Xuezhikang can effectively regulate the atherosclerosis-related factors, control the inflammatory reaction, protect the endothelial cells, and inhibit the development of ARAS.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.1;R692

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