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Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ ) and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) on the transforming growth factor-β1 (TGF-β1) synthesis and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression of in vitro cultured hepatic stellate cells (HSCs). Methods HSC-T6 rat hepatic stellate cell line was selected as the study model of the activated hepatic stellate cells. Cultured HSCs were randomized into control group, Ang Ⅱ group, AT1RA group and Ang Ⅱ AT1RA group. Cell culture medium was used to detect the TGF-β1 level by ELISA method. HSCs were harvested to measure the TIMP-1 mRNA expression by RT-PCR. Results TGF-β1 level of control group, Ang Ⅱ group and AngⅡ AT1RA group in cell culture medium was (7.531 ±0. 654) pg/mL, (9. 855± 1. 485)pg/mL and (7.719 ± 0.329) pg/mL respectively, Ang Ⅱ group higher than control group (P ＜ 0.05 ), Ang Ⅱ AT1RA group lower than Ang Ⅱ group (P ＜ 0. 05 ). TIMP-1 mRNA expression level of control group, Ang Ⅱ group and Ang Ⅱ AT1RA group in HSCs was 3. 387 ± 0. 042, 4.870 ± 0.061 and 3. 837 ± 0. 042 respectively, Ang Ⅱ group higher than control group ( P ＜ 0. 05 ), Ang Ⅱ AT1RA group lower than Ang Ⅱ group (P ＜ 0. 05). Conclusion AngiotensinⅡ can increase the TGF-β1 synthesis and TIMP-1 mRNA expression of hepatic stellate cells, while all these effects are inhibited by angiotensinⅡ type 1 receptor antagonist.
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Objective To investigate the effects of rapamycin on renal tissue and function of rats with protein overload nephropathy and to explore the protective mechanism of losartan. Methods Experimental rat models with protein overload nephropathy, induced by intraperiotoneal injection of BSA (2. 0 g/d)into female Wistar rats, were divided into three groups: control group, rapamycin group(injected intraperitoneally with rapamycin) and losartan group(injected intraperitoneally with rapamycin and given orally with losartan). At different time points, the quantity of 24-hour urine protein and renal function were measured, and the morphologic changes of renal tissues were evaluated by HE staining and electron microscope. Results Both at day 7 and day 14, rats received BSA developed intense proteinuria. At day 7, compared with control group, 24-hour proteinuria increased markedly in rapamyein group (P<0.05). Nevertheless,proteinufia was notably alleviated in losartan group (P<0.05). At day 14, 24-hour-urine protein of rapamycin group was also significantly higher than that of the losartan group (P<0.05), but therewas no significant difference between control group and losartan group (P>0.05). Proteinuria and intratubular albumin cast formation were alleviated notably in losartan group. The fusion of focal podocytes in rapamycin group was obvious in comparison with control group. Conclusions Rapamycin can agrravate proteinuria in rats with protein overload nephropathy through changing the barrier of glomerular filtration by damaging podocytes. Furthermore, losartan can alleviate severe proteinuria induced by rapamycin.
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0.05).CONCLUSION:Both group showed approved antihypertensive efficacy,with Coaprovel group showing higher efficacy than in Hyzaar group;and both group showed improvement in allorhythmia.Both group showed low incidences of adverse effect but good tolerance.
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Aim To observe the protective effect of valsartan,benazepril and combination valsartan withbenazepril on cardiac damage in rats with chronic renal failure and explore the mechanism.Methods Forty Sprague Dawley male rats were selected,and were performed five-sixths nephrectomy to produce chronic renal failure model.Two weeks after the surgery,the rats were divided randomly into model group,valsartan group,benazepril group and both valsartan and benazepril group,and a sham group was established as control group.Systolic blood pressure,BUN and serum creatinine was measured at 10 week after operation,then all rats were killed to take the hearts for pathological histological observation.The transcription of endothelin-1(ET-1 )mRNA and nitricoxide synthase (eNOS-3) mRNA in myocardium was examined by hybridization in situ.Results Systolic pressure,heart weight,heart weight index,left ventricular weight mass(LVWM) and left ventricular weight mass index(LVWMI) in model group increased significantly at 10 week after operation. Systolic pressure,heart weight,heart weight index,LVWM and LVWMI decreased markedly in rats with five-sixths nephrectomy by valsartan and/or benazepril (P
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Aim ① To observe the relationship between TGF?_1 and diabetic nephropathy in experimental rats;② To explore the effects of ACEI-fosinopril and ATRA-losartan on renal TGF?_1 in diabetic rats and their renoprotective mechanism. Method Four groups of rats were studied, A group:normal control rats;B group: strephtozotocin induced diabetic rats;C group:diabetic rats treated with fosinopril;D group: diabetic rats treated with losartan.Blood glucose, urinary excretion rates of albumin, TGF?_1,as well as the expressions of TGF?_1 protein and TGF?_1 mRNA in renal cortex and the relative kidney were measured. Result ① The urinary excretion rates of albumin and TGF?_1 in B,C ,D groups were significant higher than those in A group, fosinopril and losartan can decrease the urinary excretion rates of the two proteins but can’t make the rate normal. ② The expressions of TGF?_1 protein in renal cortex in B group was much higher than that in other 3 groups, fosinopril and losartan can inhibit the expression of TGF?_1. ③ The expressions of TGF?_1 mRNA in renal cortex increased greatest in B group, fosinopril and losartan can low the expression. Conclusion The overexpression of TGF?_1 protein and mRNA in renal cortex of diabetic rats may be one of the mechanisms of diabetic nephropathy. Fosinopril and losartan can suppress the expressions of TGF?_1 protein and mRNA in renal cortex, decrease the urinary excretion rates of TGF?_1. So alleviate the patholochanges in kidney.
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Objective To investigate the effects of losartan on unstable angina (UA).Methods In a period of 14 days, 83 subjects with UA were randomly divided into 2 groups (group T and C). In group C, nitroglycerin 10-20mg plus 5%glucose 250ml was given by vein drips twice daily. Aspirin 150mg/day and metoprolol 12.5～25mg twice daily were given too. In group T, losartan, in a single dose of 50mg/day was given in addition to treatments of group A. Frequency of angina pectoris, rate pressure product, ST segments changes in 12 lead ECG and several heart function indexes in echocardiography were investigated at the beginning and the end of the study.Results The differences of efficacy between the two groups were significant ( P
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Objective To investigate the mechanisms of angiotensinⅡ receptor blockade in protection against kidney lesion in hypertensive rats.Methods The investigation was comprised with normotensive control (WKY) and hypertensive group (SHR) which included treated and untreated group. Relevant index such as blood pressure and ultrastructural changes in glomerulus with transmission electronic microscope were acquired in three-month old and eight-month old. Losartan was administrated with 20mg?Kg -1 ?d -1 in treated group.Results The volume density of vessel endothelium, mesangial cells and mesangial area of SHR was significantly larger than that of WKY(P
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The plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET) were assayed in 76 patients with diabetic nephropathy (DN) and 23 healthy subjects, and the changes of CGRP and ET levels after treatment with angiotensin Ⅱ receptor antagonist (ARBS) were observed. The results showed that CGRP level was increased and ET level decreased after treatment with ARBS, which seemed to delay the onset and development of DN.