【摘要】 目的 觀察百草枯中毒大鼠腎組織中血紅素氧合酶1(HO1)的表達(dá),探討其病理生理機制。 方法 SD大鼠126只隨機分為空白對照組、中毒組和褪黑素組,各42只。中毒組、褪黑素組予以百草枯(25 mg/kg)腹腔注射染毒,對照組予以等量生理鹽水腹腔注射,15 min后褪黑素組予以褪黑素(10 mg/kg)腹腔注射,對照組、中毒組予以等量生理鹽水腹腔注射。于1、3、6、12 h,1、2、3、5 d時各組隨機取6只處死。蘇木精〖CD3/5〗伊紅（HE）染色觀察各組腎組織病理學(xué)變化,采用免疫組識化學(xué)和RTPCR觀察腎組織HO1蛋白和mRNA表達(dá)。 結(jié)果 ①與對照組相比,中毒組染毒后3 h即可見充血、水腫及空泡變性等病理變化,1 d達(dá)頂峰,病理損傷評分3.30±0.31(P lt;0.05),其后緩解趨勢不明顯；而褪黑素組病理變化明顯減輕且緩解趨勢明顯,1 d時病理損傷評分2.70±0.26,與中毒組相比差異有統(tǒng)計學(xué)意義(P lt;0.05)。②與對照組相比,中毒組染毒3 h在皮質(zhì)部腎小管上皮細(xì)胞的細(xì)胞膜及細(xì)胞漿HO1呈陽性表達(dá),免疫組識化學(xué)評分(IHS)3.33±1.75,HO1 mRNA表達(dá)增強,與對照組相比差異有統(tǒng)計學(xué)意義(P lt;0.05),1 d達(dá)頂峰,HIS為7.00±2.00,之后減弱,5 d仍有陽性表達(dá),但與對照組相比差異無統(tǒng)計學(xué)意義(P gt;0.05)；褪黑素組HO1表達(dá)較中毒組明顯增強,IHS評分6 h~3 d差異具有統(tǒng)計學(xué)意義(P lt;0.05),5 d不再有統(tǒng)計學(xué)意義(P gt;005)。 結(jié)論 HO1在百草枯中毒大鼠腎組織中呈高表達(dá),褪黑素能明顯改善百草枯中毒腎臟病理損傷,增強HO1表達(dá)可能是其作用途徑之一,而氧化損傷可能是百草枯中毒腎損傷病理生理機制之一。
【Abstract】 Objective To investigate the expression of heme oxygenase1 (HO1) in paraquartinduced renal injury in rats and the protective effects of melatonin, and explore possible mechanism of paraquartinduced renal injury. Methods One hundred and twentysix adult healthy SpragneDawley rats were randomly divided into three groups and 42 in each group: control group (A), paraquart group (B), and melatonin group (C). The rats in group B and group C were treated with paraquart (25 mg/kg) intraperitoneally, the rats in group A were treated with the same dose of normal saline. In 15 minutes, the rats in group C were given melatonin intraperitoneally at a dose of 10 mg/(kg·d) and the rats in group A and B were treated intraperitoneally with the same dose of normal saline. Six rats in each group were randomly sacrificed at one, three, 12 hours and one, tou, three, five days respectively. Renal histopathological changes were observed under light microscope by HE staining. The protein and mRNA expressions of HO1 were evaluated by immunohistochemical staining and RTPCR respectively. Results ①In group B, there were obvious lesions in the renal tubule of cortical part, including edema, congestion and vacuolar degeneration. These pathologic changes gradually reached the peak on the first day and did not relieved till the end of this study, the pathologic injury score was 3.30±0.31, and there was a statistical significance between group B and group A (P lt;0.05). The aforementioned pathological lesion was more palliative in group C, the pathologic injury score was 2.70±0.26 at the first day; Compared with group B, there was a statistical significance. ②In group A, there was no or weak expression of HO1 and HO1 mRNA. At the third hour, the expression of HO1 in group B was observed in the membrane and cytoplasm of renal tubular epithelial cell of cortical part. Immunohistochemistry score (IHS) was 3.33±1.75 and the expression of HO1 mRNA increased, there was a statistical significance between group B and group A (P lt;0.05). It reached the peak on the first day, IHS was 7.00±2.00, but there was no statistical difference between group B and group A on the fifth day (P gt;0.05); Compared with group B, the expression in group C was enhanced obviously, IHS were higher obviously on the six hour till to the third day (P lt;0.05), but there were no statistical differences on the fifth day (P gt;0.05). Conclusion The expression of HO1 in the paraquartdamaged kidney increases and melatonin surely has an protective effect by increasing the expression of HO1, which suggests that oxidative injury might be the main mechanism of paraquartinduced renal injury.

引用本文： 劉芙蓉,張?zhí)烀?佟飛. 血紅素氧合酶1在百草枯中毒腎臟中的表達(dá)及褪黑素對其的影響. 華西醫(yī)學(xué), 2010, 25(4): 689-. doi: 復(fù)制

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