罗勒提取物对肾血管性高血压大鼠的降压作用及其作用机制的研究
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摘要
目的:通过验证罗勒(全草)提取物(OBL)对肾性高血压模型大鼠的降压作用,探讨OBL的降压作用机理。方法:正常SPrague一Dawley(SD)大鼠适应性喂养一周后测基础血压。然后进行左肾动脉狭窄手术。手术后4周,形成两肾一夹(2K1C)肾性高血压。将高血压大鼠60只随机分成5组:罗勒(全草)提取物高(H,400mg/kg)剂量组、罗勒(全草)提取物中(M,200mg/kg)剂量组、罗勒(全草)提取物低(L,100mg/kg)剂量组、卡托普利组(Cap,30ml/kg)、高血压模型组(Model)。外加假手术组(Sham),每组12只。从肾动脉狭窄手术后4周开始灌胃给于相应药物。持续4周,每周末测血压;第4周末留24小时尿测尿肌酐(Scr)和尿素氮(Bun)活力,并处死动物取血测血管紧张素Ⅱ(AngⅡ)、内皮素(ET)、超氧化物歧化酶(SOD)、丙二醛(MDA);同时观察心脏和肾脏血管组织学改变。结果:两肾一夹(2K1C)术后4周,与假手术组(138±2.04mmHg)比高血压模型组(Model)(201±3.69mmHg)血压明显升高(P<0.05)。同时血管紧张素Ⅱ(AngⅡ)、内皮素(ET)、丙二醛(MDA)含量以及尿肌酐(Scr)和尿素氮(Bun)活力明显增高;而超氧化物歧化酶(SOD)活性降低。给予罗勒提(全草)取物后血压(收缩压和舒张压)均有下降。内皮素(ET)、丙二醛(MDA)明显下降、而超氧化物歧化酶(SOD)活性增高(P<0.05),且作用强于卡托普利组。同时,血管紧张素Ⅱ(AngⅡ)、尿肌酐(Scr)和尿素氮(Bun)也明显下降。高血压模组织学检查,各组均未见冠状动脉和肾动脉明显的病理改变。结论:罗勒(全草)提取物对肾性高血压大鼠具有降压作用,其降压作用机制可能与通过抗氧化反应来保护内皮细胞,改善血管内皮功能紊乱,抑制缩血管物质(内皮素,血栓素A2,血管紧张素Ⅱ)的释放,同时增强舒血管物质(PGI2,NO)以及调节血栓素A2(TXA2)和前列腺素(PGI2)平衡有关。
Object: To investigate the effect of the extraction of Ocimum basilicum L (OBL) on renal hypertensive rats and investigate its antihypertensive mechanism. Methods: SD rats received food and water adlibitum in 1 week of acclimation. After that baseline blood pressure (sistolic and diastolic blood pressure) was measured by noninvasive tail cuff photosensor under aseptic conditions, thirty general anesthesia rats were given a modifided 2kidney- 1clip(2K1C) operation while six rats were sham-operated (the animals received identical treatment without left renal artery ligation). Four weeks later, tweniyfour hypertensive rats were randomly allocated to four groups such as OBL (higher, 400mg/kg), OBL(midel, 200mg/kg), OBL(lower, 100mg/kg), captopril (cap, 30ml/kg) and model group after allocation, the treatment period was 4 weeks. The blood pressure was measured weekly. In the 4th week, blood urea nitrogen(Bun) and serum creatinine (Scr) were measured too. At sacrifice, blood was harvested to measure the levels of angiotensinⅡ(AngⅡ), superoxide dismutase (SOD), malonaldehyde(MDA) and endotnelin (ET) at the end of the 4th week. Kidneys and hearts were collected to observe the patho1ogical changes of arteriole too. Results: Four weeks after 2K1C operation, the blood pressure of the 2kidney- 1clip operation group increased significantly(138±2.04 mmHg vs 201±3.69 mmHg of sham group, P<0.05). and the levels of angiotensinⅡ(AngⅡ), malonaldehyde (MDA), endotnelin (ET), blood urea nitrogen (Bun) and serum creatinine (Scr) was slightly increased in plasma. Superoxide dismutase (SOD) was decreased significantly. Treated with captopril and Ocimum basilicum L (OBL), the blood pressure(sistolic blood pressure and diastolic blood pressure) decreased significantly and continually (P<0.05). During the course of administration, the levels of angiotensinⅡ(AngⅡ), malonaldehyde (MDA) and endotnelin (ET), blood urea nitrogen (Bun) and serum creatinine(Scr) was slightly decreased in plasma. mean while, superoxide dismutase (SOD) in plasma increased respeetively(P<0.05). In OBL groups, due to the short course of experiment, the pathological change of coronary artery and renal artery was not seen under the microscope. Conclusions: Ocimum basilicum L (OBL) can reduce the blood pressure of the renal hypertensive rat, Which is likely related to throu the antioxidate rection, to improve the blood vessel endothelium function and inhibited the material of vessel contraction release. It should be more than one antihypertensive target of Ocimum basilicum L (OBL).
Object: To investigate the effect of the extraction of Ocimum basilicum L (OBL) on renal hypertensive rats and investigate its antihypertensive mechanism. Methods: SD rats received food and water adlibitum in 1 week of acclimation. After that baseline blood pressure (sistolic and diastolic blood pressure) was measured by noninvasive tail cuff photosensor under aseptic conditions, thirty general anesthesia rats were given a modifided 2kidney- 1clip(2K1C) operation while six rats were sham-operated (the animals received identical treatment without left renal artery ligation). Four weeks later, tweniyfour hypertensive rats were randomly allocated to four groups such as OBL (higher, 400mg/kg), OBL(midel, 200mg/kg), OBL(lower, 100mg/kg), captopril (cap, 30ml/kg) and model group after allocation, the treatment period was 4 weeks. The blood pressure was measured weekly. In the 4th week, blood urea nitrogen(Bun) and serum creatinine (Scr) were measured too. At sacrifice, blood was harvested to measure the levels of angiotensinⅡ(AngⅡ), superoxide dismutase (SOD), malonaldehyde(MDA) and endotnelin (ET) at the end of the 4th week. Kidneys and hearts were collected to observe the patho1ogical changes of arteriole too. Results: Four weeks after 2K1C operation, the blood pressure of the 2kidney- 1clip operation group increased significantly(138±2.04 mmHg vs 201±3.69 mmHg of sham group, P<0.05). and the levels of angiotensinⅡ(AngⅡ), malonaldehyde (MDA), endotnelin (ET), blood urea nitrogen (Bun) and serum creatinine (Scr) was slightly increased in plasma. Superoxide dismutase (SOD) was decreased significantly. Treated with captopril and Ocimum basilicum L (OBL), the blood pressure(sistolic blood pressure and diastolic blood pressure) decreased significantly and continually (P<0.05). During the course of administration, the levels of angiotensinⅡ(AngⅡ), malonaldehyde (MDA) and endotnelin (ET), blood urea nitrogen (Bun) and serum creatinine(Scr) was slightly decreased in plasma. mean while, superoxide dismutase (SOD) in plasma increased respeetively(P<0.05). In OBL groups, due to the short course of experiment, the pathological change of coronary artery and renal artery was not seen under the microscope. Conclusions: Ocimum basilicum L (OBL) can reduce the blood pressure of the renal hypertensive rat, Which is likely related to throu the antioxidate rection, to improve the blood vessel endothelium function and inhibited the material of vessel contraction release. It should be more than one antihypertensive target of Ocimum basilicum L (OBL).
引文
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