自发性高血压大鼠肠系膜动脉重塑及咪达普利和厄贝沙坦对其的影响。
Mesenteric artery remodeling and effects of imidapril and irbesartan on it in spontaneously hypertensive rats.
作者信息
Zhu Zhong-Sheng, Wang Jin-Ming, Chen Shao-Liang
机构信息
Department of Cardiovascular Medicine, Third Affiliated Hospital of Nanjing Medical University, Nanjing 210006, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2004 May 15;10(10):1471-5. doi: 10.3748/wjg.v10.i10.1471.
AIM
To investigate the remodeling of mesenteric artery and the expression of TGF-beta1, c-Jun in mesenteric artery and effects of imidapril and irbesartan on the remodeling in spontaneously hypertensive rats (SHR).
METHODS
Thirty SHR (male/female, 21/9), aged 13 wk, were randomly divided into 3 groups (7 male rats and 3 female rats each group): SHR group, imidapril group (imidapril 3 mg/kg.d was given in drinking water for 14 wk), and irbesartan group (irbesartan 50 mg/kg.d was given in drinking water foe 14 wk). Ten homogeneous Wistar Kyoto rats, 5 males and 5 females, weighing 206+/-49 g, were selected as normal control group (WKY group). Systolic pressure was measured on d 1, 2, 4, 6, 8, 10, 12 and 14 during the experiment and the rats were killed at the end of the experiment. Angiotensin II (Ang II) level in plasma and mesenteric arteries was measured by radioimmunoassay. The morphology of the secondary branches of mesenteric artery were examined by light microscopy and electron microscopy. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of transforming growth factor TGF-beta1 and c-Jun mRNA.
RESULTS
Compared with imidapril group and irbesartan group, the blood pressure was remarkably increased in SHR group. Ang II level in plasma and mesenteric arteries in SHR group was the same or lower than that in WKY group, and was higher in irbesartan group and lower in imidapril group. The remodeling of mesenteric arteries in SHR group was mostly obvious among the 4 groups. The ratio of TGF-beta1 absorbed light value to GAPDH absorbed light value in the SHR group was 0.887+/-0.019, which was significantly higher than that in WKY group, imidapril group, and irbesartan group with the ratios of 0.780+/-0.018, 0.803+/-0.005, and 0.847+/-0.017, respectively (P<0.01). Ang II level in plasma and mesenteric arteries in imidapril group was significantly lower than that in irbesartan group (P<0.05). The c-Jun absorbed light value/GAPDH absorbed light value of mesenteric arteries in the SHR group was 0.850+/-0.015, which was significantly higher than that in the WKY, imidapril, and irbesartan groups (0.582+/-0.013, 0.743+/-0.012, and 0.789+/-0.013, respectively, P<0.01), and was significantly lower in imidapril group than in irbesartan group (P<0.05).
CONCLUSION
Imidapril and irbesartan can not only control blood pressure but also inhibit mesenteric arteries remodeling and mRNA expression of TGF-beta1, c-Jun in SHR. Imidapril is more effective than irbesartan.
目的
研究自发性高血压大鼠（SHR）肠系膜动脉重塑及转化生长因子β1（TGF-β1）、c-Jun在肠系膜动脉中的表达，以及依那普利和厄贝沙坦对其重塑的影响。
方法
选取30只13周龄的SHR（雄性/雌性，21/9），随机分为3组（每组7只雄性大鼠和3只雌性大鼠）：SHR组、依那普利组（饮用含依那普利3 mg/kg.d的水14周）和厄贝沙坦组（饮用含厄贝沙坦50 mg/kg.d的水14周）。选取10只体重206±49 g的同质性Wistar Kyoto大鼠（5只雄性和5只雌性）作为正常对照组（WKY组）。在实验期间的第1、2、4、6、8、10、12和14天测量收缩压，并在实验结束时处死大鼠。采用放射免疫分析法测定血浆和肠系膜动脉中的血管紧张素II（Ang II）水平。通过光学显微镜和电子显微镜检查肠系膜动脉二级分支的形态。采用逆转录聚合酶链反应（RT-PCR）检测转化生长因子TGF-β1和c-Jun mRNA的表达。
结果
与依那普利组和厄贝沙坦组相比，SHR组血压显著升高。SHR组血浆和肠系膜动脉中的Ang II水平与WKY组相同或更低，厄贝沙坦组更高，依那普利组更低。在4组中，SHR组肠系膜动脉重塑最为明显。SHR组中TGF-β1吸光度值与甘油醛-3-磷酸脱氢酶（GAPDH）吸光度值之比为0.887±0.019，显著高于WKY组、依那普利组和厄贝沙坦组，其比值分别为0.780±0.018、0.803±0.005和0.847±0.017（P<0.01）。依那普利组血浆和肠系膜动脉中的Ang II水平显著低于厄贝沙坦组（P<0.05）。SHR组肠系膜动脉中c-Jun吸光度值/GAPDH吸光度值为0.850±0.015，显著高于WKY组、依那普利组和厄贝沙坦组（分别为0.582±0.013、0.743±0.012和0.789±0.013，P<0.01），且依那普利组显著低于厄贝沙坦组（P<0.05）。
结论
依那普利和厄贝沙坦不仅能控制血压，还能抑制SHR肠系膜动脉重塑及TGF-β1、c-Jun的mRNA表达。依那普利比厄贝沙坦更有效。
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