| It's the main mechanism to cause renal fibrosis that the cells proliferated, phynotype conversed in kidney, and increasing of extracellular matrix (ECM) production and decreasing of ECM degradation which could cause over-deposition of ECM. After phenotype conversion, the cells in kidney converted into myofibroblast (MFB) , expressed characteristic a -smooth muscle actin ( a -SMA) and secreted collagen, which caused renal fibrosis. Some study indicated that angiotensin converting enzyme inhibitor (ACEI) can inhibit interstitial fibrosis of kidney. However, angiotensin II receptor blockers (ARB) could significantly inhibit glomerulus fibrosis, which mechanism was perhaps that both of them inhibited renal cell proliferation and phenotype conversion, a -SMA and matrix synthesize, and delayed renal fibrosis and protect renal function. The present work undertaken established 5/6nephrectomy model in rats. To observe the effect of the combination of enalapril (ACEI) and valsartan (ARB) on renal fibrosis in 5/6 nephrectomy model in rats, and to explore the mechanism of them in delaying renal fibrosis, and to provide theoretical foundation of clinical treatment and experiment evidence.Methods: 54 normal Wistar rats were divided into five groups at random. Group: negative control group (n=10), perfused the same volum N.S. into stomach. Group II: positive untreated 5/6 nephrectomy group (n=10), the same treatment as group I everyday. Group III: enalapril-treated 5/6 nephrectomy group (n=11), perfused enalapril into stomach everyday, 10mg/kg/d. Group IV: valsartan-treated 5/6 nephrectomy group (n=11), perfused valsartan into stomach everyday, 30mg/kg/d. Group V: enalapril combined versartan treated 5/6 nephrectomy group (n=12), perfused enalapril 10mg/kg/d and valsartan 30mg/kg/d into stomach everyday. The experiment lasted for 12 weeks. At the second, forth, eighth, twelfth week, the weight, blood pressure were measured in rats, and the proteinuria and 24-hour creatinine clearance rate were assayed. At the twelfth week, the rats were all killed, and the kidneys were taken out, fixed and sliced, and routine pathological examination and immunohistochemical staining were carried out, and the effect of the combination of ACEI and ARB on glomerulus and interstitium expressing a -SMA and collagen IV was studied.Result:1. The blood pressure in group II was significantly higher than in group I. However, the blood pressure in group III, IV, V was significantly lower than in group II (p<0.05); and lower in group V than in group III, IV (P<0.05). There was no significant difference between group III and group IV at the fourth, eighth, twelfth week. 2. At the 12th week the mean weigh in group II was significantly lower than in group III, IV, V (P<0.05). However, the remnant renal weigh of group II was significantly higher than group III, IV, V (P<0.05), and in group III, IV was significantly higher than in group V (P<0.05). There was no significant difference between group III and group IV. 3. At the 2nd, 4th, 12th week, 24hr proteinuria excretion was assayed. The 24hr proteinuria excretion in group II was significantly higher than in group I (P<0.05), and was significantly lower in group III, IV, V than in group II(P<0.05). and was significantly lower in group V than in group III, IV (P<0.05). There was no significant difference between group III and group IV (P<0.05). 4. At the 2nd, 4th, 8th, 12th, the 24-hour creatitine clearance rate of group II rats was significantly lower than group I (P<0.05), and was significantly higher in group III, IV, V than in group II (P<0.05), and was significantly lower in group III, IV than in group V (P<0.05). There was no noted difference between III and group IV. 5. HE staining: the renal fibrosis in group II became severer than in group I, and in group III, IV, V was more gently thanin group II (P<0.05). 6. Immunohistochemical staining: the intensity of a -SMA and collagen IV immunostaining of glomerulus in group II was stronger than in group I (P<0.05). The int...
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