CAJ | 학술논문

目的观察替米沙坦对大鼠IgA肾病模型过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响,探讨替米沙坦对肾小管间质保护作用的可能机制.方法 40只雄性SD大鼠运用牛血清白蛋白(BSA)+脂多糖(LPS)+四氯化碳(CCl4)方法建立实验性IgA肾病模型,设立对照组、模型组、罗格列酮治疗组(简称罗格列酮组)、替米沙坦治疗组(简称替米沙坦组)、氯沙坦治疗组(简称氯沙坦组),分别于实验前、第4周末、第8周末、第10周末测各组大鼠24 h尿蛋白;免疫组化测定各组PPARγ、转化生长因子(TGF)β1、α-平滑肌肌动蛋白(SMA)表达;RT-PCR检测各组PPARγ、TGF-β1、单核细胞趋化因子(MCP)-1变化.结果第10周末尿蛋白量(mg)在模型组高于对照组(14.14±1.99 vs 1.59±0.18),而罗格列酮组(2.35±0.33)、替米沙坦组(1.88±0.09)、氯沙坦组(2.82±0.34)显著低于模型组(均P＜0.05),以替米沙坦组改变明显.模型组大鼠肾脏组织中存在系膜细胞增生及间质炎细胞浸润,而治疗组肾小管间质损伤减轻,罗格列酮组、替米沙坦组、氯沙坦组的损伤指数均低于模型组(1.97±0.23、1.57±0.14、2.15±0.22 vs 3.10±0.18,均P＜0.01),尤以替米沙坦组改善明显.免疫组化及RT-PCR结果显示PPARγ、TGF-β1、α-SMA及MCP-1在对照组肾小管及间质中微量表达,模型组呈高表达,氯沙坦组与模型组无明显差异,罗格列酮和替米沙坦组表达减少.结论替米沙坦可能通过激活PPARγ途径及阻断血管紧张素Ⅱ受体两种途径显示更独特的小管间质损伤的保护作用.
목적 관찰체미사탄대대서IgA신병모형과양화물매체증식물격활수체γ(PPARγ)표체적영향,탐토체미사탄대신소관간질보호작용적가능궤제.방법 40지웅성SD대서운용우혈청백단백(BSA)+지다당(LPS)+사록화탄(CCl4)방법건립실험성IgA신병모형,설립대조조、모형조、라격렬동치료조(간칭라격렬동조)、체미사탄치료조(간칭체미사탄조)、록사탄치료조(간칭록사탄조),분별우실험전、제4주말、제8주말、제10주말측각조대서24 h뇨단백;면역조화측정각조PPARγ、전화생장인자(TGF)β1、α-평활기기동단백(SMA)표체;RT-PCR검측각조PPARγ、TGF-β1、단핵세포추화인자(MCP)-1변화.결과 제10주말뇨단백량(mg)재모형조고우대조조(14.14±1.99 vs 1.59±0.18),이라격렬동조(2.35±0.33)、체미사탄조(1.88±0.09)、록사탄조(2.82±0.34)현저저우모형조(균P＜0.05),이체미사탄조개변명현.모형조대서신장조직중존재계막세포증생급간질염세포침윤,이치료조신소관간질손상감경,라격렬동조、체미사탄조、록사탄조적손상지수균저우모형조(1.97±0.23、1.57±0.14、2.15±0.22 vs 3.10±0.18,균P＜0.01),우이체미사탄조개선명현.면역조화급RT-PCR결과현시PPARγ、TGF-β1、α-SMA급MCP-1재대조조신소관급간질중미량표체,모형조정고표체,록사탄조여모형조무명현차이,라격렬동화체미사탄조표체감소.결론 체미사탄가능통과격활PPARγ도경급조단혈관긴장소Ⅱ수체량충도경현시경독특적소관간질손상적보호작용.
Objective To observe the effect of telmisartan on the expression of PPARγin rat renal tissue of IgA nephropathy model and clarify the possible mechanism of telmisartan in tubulointerstitial injury.Methods The experimental rat model with IgA nephropathy was induced by bovine serum albumin ( BSA),lipopolysaccharide(LPS)and carbon tetrachloride(CCl4). Forty male SD rats were randomly divided into control group, IgA model group, rosiglitazone group, telmisartan group and losartan group. At preadministration, Weeks 4, 8 and 10, the quantity of 24-hour proteinuria was measured. The morphologic changes of renal tissues were evaluated by electron microscope. Immunohistochemistry was used to observe the expressions of PPARγ, TGF-β1 and α-smooth muscle actin (α-SMA) in different groups and RT-PCR to detect the expressions of PPARγ, TGF-β1 and monocyte chemoattractant protein-1 ( MCP-1 ) in different groups. Results Compared with control group, 24-hour proteinuria(mg) increased markedly in IgA model group( 14. 14 ± 1.99 vs 1.59 ±0. 18), but rosiglitazone group(2. 35 ±0. 33), telmisartan group( 1.88 ±0. 09)and losartan group( 2. 82 ± 0. 34 ) was much lower and telmisartan had the most significant effect (all P <0. 05). Compared with control group, there were varying degrees of mesangial proliferation and infiltration of inflammatory cell in IgA model group(3. 10 ±0. 18). The tubulointerstitial injury was notably alleviated in rosiglitazone group( 1.97 ±0. 23), telmisartan group( 1.57 ±0. 14) and losartan group (2. 15 ±0. 22) while telmisartan had the most significant effect (all P < 0.01 ＝. With immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), PPARγ, TGF-β1, α-SMA and MCP-1 had minimal expression on tubule and interstitium in normal group. But there was a high expression in model group. There was no difference between losartan and model groups. There was a lowered expression in rosiglitazone and telmisartan groups. Conclusion Possibly through two separate passways of stimulating PPARγ and preventing Angiotensin Ⅱ receptor, telmisartan shows special protective function in tubulointerstitial injury.