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目的建立肾动脉狭窄性高血压模型猴,并制定其评价标准。方法制作肾血管狭窄性高血压模型猴的三种方法分别称2肾1窄型(2K1C)法,2肾2窄型(2K2C)法及1肾1窄型(1K1C)法(本次未涉及此法)。①2K1C模型5～10岁食蟹猴麻醉后右侧卧位放平,在左肾部位处10×15 cm范围去毛,常规消毒后从左侧肋骨下缘往下,沿脊柱旁4.5～5 cm处皮肤做约5 cm长的切口,分离皮下组织和腰背筋膜,切开内斜肌盘膜,推开背长肌,切开腹壁进入腹腔后细心分离肾脏外围的脂肪组织以暴露肾脏。找到肾门处,在此处由下往上有三条管,依次为输尿管、肾静脉及肾动脉。小心地钝性分离出一段肾动脉,选用一定直径的银夹(钳环)套在肾动脉上然后夹牢以造成肾动脉狭窄(6～8 kg猴用直径为0.8～1.0 mm的银环)。依次缝合腹膜壁层、肌肉及皮肤创口。术后1周内皮下注射青霉素G 3～6万U.d-1以预防伤口感染。②2K2C模型当2K1C模型不够理想(血压不够高)时,可以对另一侧好肾实施动脉缩窄术(具体手术方法同2K1C模型制作),以使其血压升高到理想的高度(收缩压、舒张压均应升高80%以上)。判断的时间以第2次术后1.5个月左右为宜。结果①2K1C模型(n=4):术后2周血压开始升高,4周后血压升高达峰值(收缩压、舒张压均升高50%以上),随后稍降(10%),接下来大多数稳定并长期维持下去。②2K2C模型(n=4):术后2周血压开始升高,4周后血压升至峰值(收缩压、舒张压均升高80%以上),随后稍降并长期维持。③肾素活性变化情况:手术前后血中肾素将发生明显变化(正在以ELISA试剂盒法等探索其可靠的检测方法)。④评价标准:2K1C模型血压稳定后收缩压、舒张压均应比术前升高50%以上;而2K2C模型的血压稳定后收缩压、舒张压均应比术前升高80%以上。结论肾动脉狭窄性高血压模型猴因其形成过程涉及肾素-血管紧张素系统,加之猴子基因与人类基因有93%以上的相似度,故该高血压模型更接近于临床原发性高血压从而更适合于包括肾素抑制剂及血管紧张素转化酶抑制剂在内的抗高血压药的药效学关联的实验研究。
Objective To establish a rat model of renal artery stenosis hypertension and develop its evaluation criteria. Methods Three methods of making a rabbit model of renal vascular stenosis were named 2K1C, 2K2C and 1K1C, respectively This method). ① 2K1C model 5 to 10-year-old cynomolgus right lateral decubitus anesthesia in the left kidney at 10 × 15 cm range to hair removal, routine disinfection from the lower edge of the left rib down along the spine 4.5 ~ 5 cm The skin is about 5 cm long incision, the separation of subcutaneous tissue and back fascia, incision of the hypothalamic muscle of the hypothalamus, open the abdominal wall into the abdominal cavity carefully isolated fat tissue around the kidney to expose the kidneys. Find the kidney door, where there are three from the bottom of the tube, followed by the ureter, renal vein and renal artery. Carefully blunt dissection of a section of renal artery, use a certain diameter of the silver clip (clamp ring) set in the renal artery and then clip to cause renal artery stenosis (6 ~ 8 kg monkey with a diameter of 0.8 ~ 1.0 mm silver ring) . Followed by peritoneal suturing, muscle and skin wounds. Subcutaneous injection of penicillin G 3 ~ 60000 U.d-1 within 1 week after operation to prevent wound infection. 2K2C model When 2K1C model is not ideal (blood pressure is not high enough), the other side of the kidney can be artificially narrowed (specific surgical methods with 2K1C model making) to make its blood pressure to the desired height (systolic blood pressure, Diastolic blood pressure should be increased by more than 80%). Time to judge the second 1.5 months after surgery is appropriate. Results ①K1C model (n = 4): The blood pressure began to rise at 2 weeks after operation and peaked at 4 weeks (the systolic and diastolic blood pressures increased more than 50%), then decreased slightly (10% Most stable and long-term maintenance. ②2K2C model (n = 4): blood pressure began to rise 2 weeks after surgery, 4 weeks after the peak blood pressure (systolic blood pressure, diastolic blood pressure increased by more than 80%), then slightly lower and long-term maintenance. Changes in renin activity: Changes in blood renin will occur before and after surgery (ELISA kit method is being explored to ensure its reliable detection method). ④ Evaluation criteria: 2K1C model stable blood pressure systolic blood pressure and diastolic blood pressure should be increased by 50% or more than preoperative; and 2K2C model blood pressure stabilized systolic blood pressure, diastolic blood pressure should be higher than preoperative 80%. Conclusion The model of renal artery stenosis hypertrophy involves the renin-angiotensin system in the process of genesis, and the homology of the monkey gene with that of the human gene is more than 93%. Therefore, the model of hypertension is more similar to that of clinical essential hypertension Which is more suitable for the experimental study of pharmacodynamic effects of antihypertensive drugs including renin inhibitors and angiotensin-converting enzyme inhibitors.