Pan Yue-juan, Tao Zhong-fei, Wang Qian, Lu Min, Guan You-fei, Zhu Yi, Wang Yue
Department of Nephrology, Peking University Third Hospital, Beijing 100191, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2011 Dec 18;43(6):820-6.
To investigate renal expression of soluble epoxide hydrolase (sEH) in 2-kidney-1-clip rats and explore the role of sEH in renal arterial stenosis hypertensive development.
Hypertensive models were established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. In the study,16 male Sprague-Dawly rats were randomized into sham operation group and 2-kidney-1-lip (2K1C) group (n=8, each group), and were observed for 40 days. Before operation and every ten days after operation, systolic blood pressure (SBP) was measured and twenty-four-hour urine was collected. At the end of the observation, the blood and kidneys were harvested. The serum Na,24-hour urine protein excretion were measured. Renin activity and angiotensin II concentrition in plasm and renal tissue were evaluated by radioimmunoassay (RIA).The expression of sEH, peroxisome proliferator-activated receptor-γ (PPARγ) in kidneys were assessed by immunohistochemistry and Western blotting. Histology was analysed after kidney sections were stained by Grocott-Gomori methenamine-silver nitrate.
After surgery, the systolic blood pressure in 2K1C group gradually became higher than that in sham group. Urine protein excretion was statistically increased in 2K1C group on the 30 th and 40 th days, while serum sodium was of no significant difference from those of the two groups. Renin-angiotensin system in both clipped and nonclipped kidneys were also invoked by the 2K1C surgery. Both sEH and PPARγ were upregulated in renocortex and renomedulla in 2K1C group. The two groups were compared: in SBP,on the 10 th day, (106.70±7.71) vs.(124.04±6.79) mmHg, P<0.001,and on the 40 th day,(107.80±10.01) vs. (150.40±11.76) mmHg, P<0.001; Urine protein excretion,on the 30 th day,(206.81±37.61)vs.(292.33±20.53)mg/d, P=0.005; Serum sodium, (179.76±29.20) vs. (157.72±51.00)mmol/L, P=0.44; Renin activity[plasm(50.00±13.66) vs.(132.90± 31.22)ng/(L×h),P=0.03; clipped kidney(128.40±36.88)vs.(324.90±56.66)ng/(g×h), P=0.01; nonclipped kidney(103.00±19.87)vs.(345.10±42.68)ng/(g×h), P<0.001]; Ang II [plasm(4 810.00±1 164.00)vs. (10 470.00±1 760.00) ng/L,P=0.02, clipped kidney(735.90±154.40)vs.(2 094.00±372.20)ng/g, P=0.005, nonclipped kidney(648.10±217.90)vs.(1 774.00±206.60)ng/g, P=0.002]; the expression of sEH (sEH/β-actin) in renocortex [clipped kidney (0.33±0.08) vs. (1.73±0.12), P<0.001, nonclipped kidney (0.43±0.09)vs. (0.70± 0.05), P=0.04]; the expression of PPARγ (PPARγ/β-actin) in renocortex [clipped kidney(0.17±0.05) vs. (0.89±0.11), P=0.002, and nonclipped kidney(0.27±0.07) vs. (0.56±0.07), P=0.04]. Clipped kidney showed more severe glomerulosclerosis and tubular atrophy in 2K1C group than in sham group.
sEH probably plays an important role in the development of hypertension in the rat models of renovascular hypertension. The activation of PPAR-γ and RAAS by renal arterial stenosis are associated with sEH upregulation, suggesting that they might regulate sEH expression and take part in hypertensive development.
研究2肾1夹大鼠肾脏中可溶性环氧化物水解酶（sEH）的表达情况，并探讨sEH在肾动脉狭窄性高血压发展过程中的作用。
通过慢性部分结扎左肾动脉，在斯普拉格-道利大鼠中建立高血压模型。本研究中，将16只雄性斯普拉格-道利大鼠随机分为假手术组和2肾1夹（2K1C）组（每组n = 8），观察40天。术前及术后每10天测量收缩压（SBP），并收集24小时尿液。观察结束时，采集血液和肾脏。检测血清钠、24小时尿蛋白排泄量。采用放射免疫分析法（RIA）评估血浆和肾组织中的肾素活性及血管紧张素II浓度。通过免疫组织化学和蛋白质免疫印迹法评估肾脏中sEH、过氧化物酶体增殖物激活受体-γ（PPARγ）的表达。肾脏切片经Grocott-Gomori六胺银染色后进行组织学分析。
术后，2K1C组的收缩压逐渐高于假手术组。2K1C组在第30天和第40天的尿蛋白排泄量有统计学意义的增加，而两组的血清钠无显著差异。2K1C手术也激活了夹闭肾和未夹闭肾的肾素-血管紧张素系统。2K1C组肾皮质和肾髓质中的sEH和PPARγ均上调。两组比较：SBP方面，第10天，（106.70±7.71）与（124.04±6.79）mmHg，P<0.001；第40天，（107.80±10.01）与（150.40±11.76）mmHg，P<0.001；尿蛋白排泄量方面，第30天，（206.81±37.61）与（292.33±20.53）mg/d，P = 0.005；血清钠方面，（179.76±29.20）与（157.72±51.00）mmol/L，P = 0.44；肾素活性[血浆（50.00±13.66）与（132.90±31.22）ng/（L×h），P = 0.03；夹闭肾（128.40±36.88）与（324.90±56.66）ng/（g×h），P = 0.01；未夹闭肾（103.00±19.87）与（345.10±42.68）ng/（g×h）），P<0.001]；血管紧张素II[血浆（4810.00±1164.00）与（10470.00±1760.00）ng/L，P = 0.02，夹闭肾（735.90±154.40）与（2094.00±372.20）ng/g，P = 0.005，未夹闭肾（648.10±217.90）与（1774.00±206.60）ng/g，P = 0.002]；肾皮质中sEH（sEH/β-肌动蛋白）的表达[夹闭肾（0.33±0.08）与（1.73±0.12），P<0.001，未夹闭肾（0.43±0.09）与（0.70±0.05），P = 0.04]；肾皮质中PPARγ（PPARγ/β-肌动蛋白）的表达[夹闭肾（0.17±0.05）与（0.89±0.11），P = 0.002，未夹闭肾（0.27±0.07）与（0.56±0.07），P = 0.04]。2K1C组中夹闭肾的肾小球硬化和肾小管萎缩比假手术组更严重。
sEH可能在肾血管性高血压大鼠模型的高血压发展中起重要作用。肾动脉狭窄激活PPAR-γ和RAAS与sEH上调有关，提示它们可能调节sEH表达并参与高血压发展。
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