胰激肽原酶对自发性高血压大鼠肾脏结构与功能的保护作用

Nephro-protective effects of pancreatic kininogenase on function and morphology in spontaneously hypertensive rats

目的:观察胰激肽原酶干预对自发性高血压大鼠(SHR)肾脏结构与功能的影响,探讨激肽释放酶-激肽系统在高血压及肾脏保护方面的作用。方法:12只36周龄SPF级雄性SHR随机分成2组,治疗组给予胰激肽原酶(800U/kg/d)灌胃治疗12周,观察大鼠血压、血肌酐(Scr)、尿素氮(BUN)及尿微量白蛋白(mALB)、尿β2微球蛋白(β2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)浓度及肾脏组织病理改变,并用逆转录-聚合酶链反应(RT-PCR)方法测定肾皮质组织型激肽释放酶 mRNA的表达。结果:较之SHR对照组胰激肽原酶治疗后血压明显下降(P<0.01);尿mALB、β2-MG、NAG定量明显降低(P<0.01);肾皮质组织型激肽释放酶 mRNA表达水平增加(P<0.05)。病理上SHR对照组大鼠肾小球小动脉管壁增厚,管腔狭窄,个别小球硬化;胰激肽原酶治疗组肾小动脉结构正常,未见肾动脉硬化。结论:胰激肽原酶能显著减少尿微量蛋白、逆转肾小动脉硬化改变,保护肾功能,其机制可能与降低血压,增加肾脏中组织激肽释放酶水平有关。

Objective： To study the effect of pancreatic kininogenase on renal structure and function in spontaneously hypertensive rat （SHR） and explore the role of kallikrein-kinin system in the development of hypertension and nephro-protection. Methods： The 12 cases of 36 week-old male SHRs were gorged with pancreatic kininogenase （800U/kg · d, n=6） or distilled water respectively for 12 weeks in treating and control groups. The blood pressure, the microalbumin （mALB）, beta2 - microglobin （β2 - MG）, N- acetyl- β- D- glucosaminidase （NAG） were assessed, and renal tissues were examined routinely by light and electronic microscopy. The levels of tissue kallikrein mRNA were detected by RT-PCR. Results： The levels of SBP significantly decreased after treatment of pancreatic kininogenase （P〈0. 01）, the excretion of mALB, β2- MG and NAG in urine significantly decreased in the treating group compared to control group （P〈0.01）. The levels of tissue kallikrein mRNA expression in the kidneys increased after administration in the treating group （P〈0.05） . Severe hypertrophy and sclerosis on the walls of arterioles, narrow in the lumina of these arterioles and hyalinization in some glomeruli were seen in control SHR. Pancreatic kininogenase could attenuate the above damages of small arteries. There was no arterial arteriolsclerosis in treating group. Conclusion.. Pancreatic kininogenase reduces the extent of proteinuria and attenuates functional and structural damage induced by hypertension. The decrease of SBP and increase of tissue kallikrein may be involved in the mechanism concerned.