【摘要】 目的 觀察百草枯中毒大鼠腎組織中血紅素氧合酶1(HO1)的表達,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變化,采用免疫組識化學和RTPCR觀察腎組織HO1蛋白和mRNA表達。 結果 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達頂峰,病理損傷評分3.30±0.31(Plt;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計學意義(Plt;0.05)。②與對照組相比,中毒組染毒3 h在皮質部腎小管上皮細胞的細胞膜及細胞漿HO1呈陽性表達,免疫組識化學評分(IHS)3.33±1.75,HO1 mRNA表達增強,與對照組相比差異有統計學意義(Plt;0.05),1 d達頂峰,HIS為7.00±2.00,之后減弱,5 d仍有陽性表達,但與對照組相比差異無統計學意義(Pgt;0.05)；褪黑素組HO1表達較中毒組明顯增強,IHS評分6 h~3 d差異具有統計學意義(Plt;0.05),5 d不再有統計學意義(Pgt;005)。 結論 HO1在百草枯中毒大鼠腎組織中呈高表達,褪黑素能明顯改善百草枯中毒腎臟病理損傷,增強HO1表達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 oxygenase1 (HO1) in paraquartinduced renal injury in rats and the protective effects of melatonin, and explore possible mechanism of paraquartinduced renal injury. Methods One hundred and twentysix adult healthy SpragneDawley 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 HO1 were evaluated by immunohistochemical staining and RTPCR 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 (Plt;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 HO1 and HO1 mRNA. At the third hour, the expression of HO1 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 HO1 mRNA increased, there was a statistical significance between group B and group A (Plt;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 (Pgt;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 (Plt;0.05), but there were no statistical differences on the fifth day (Pgt;0.05). Conclusion The expression of HO1 in the paraquartdamaged kidney increases and melatonin surely has an protective effect by increasing the expression of HO1, which suggests that oxidative injury might be the main mechanism of paraquartinduced renal injury.
【摘要】 目的 探討口服百草枯中毒患者口腔護理的方法及早期護理的臨床意義。 方法 2009年1月-2010年3月，采用半隨機方法將62例白草枯中毒患者按中毒時間的長短分A組（中毒時間lt;3 d，n=32）、B組（中毒時間gt;3 d，n=3），比較兩組患者口腔潰瘍的治愈率、并發癥發生狀況，分析早期口腔護理的必要性。 結果 A組患者百草枯所致的口腔黏膜損害明顯減輕，并發癥發生率降低，為改善預后提供了條件，顯示了早期加強口腔護理的成效。 結論 重視百草枯早期口腔護理，能夠減輕口腔糜爛潰瘍痛苦，減少并發癥，提高患者生活質量。【Abstract】 Objective To investigate the clinical significance of early oral care for paraquat-poisoned patients. Methods A quasi-randomized controlled trial was used. A total of 62 paraquat-poisoned patients (from January 2009 to March 2010) were divided into experimental group and control group in order to compare the healing rate of oral ulcer, complications and the necessity of early oral care between the two groups. Results The oral mucosa lesions in experimental group obviously alleviated and the complications decreased. The effective early oral care provided the very favorable conditions for better prognosis. Conclusion The early oral care for paraquat-poisoned patients could relieve the pain of oral ulcer, reduce the complications and improve patient′s life quality.
ObjectiveTo investigate the endoplasmic reticulum stress associated apoptosis gene Caspase-12 expression in paraquat-induced pulmonary fibrosis.
Methods30 adult healthy Sprague-Dawley(SD) rats were randomly divided into a nomal control group,two pulmonary fibrosis model groups (intragastrically administered paraquat for 14 days and 28 days,respectively).The model of pulmonary fibrosis was established through intragastrically administering paraquat at the dose of 30 mg/kg.RT-PCR was used to determine the mRNA expression of Caspase-12.Immunohistochemistry was used to determine the protein expression of Caspase-12.HE staining and Masson staining were used to determine the degree of alveolitis and pulmonary fibrosis.
ResultsHE staining and Masson staining of lung tissues proved that pulmonary fibrosis model was successfully constructed.The degree of alveolitis and pulmonary fibrosis in the model group was significantly more serious than that in the control group(P<0.01).RT-PCR and Immunohistochemistry results showed that the expression of Caspase-12 were remarkably increased in the pulmonary fibrosis model group(14 d group)(P<0.01),even more elevated in 28 d group compared with the 14 d group.
ConclusionThe results demonstrate that the expression of Caspase-12 in paraquat poisoned rats is up-regulated,suggesting endoplasmic reticulum stress plays an important role in paraquat induced-pulmonary fibrosis.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
ObjectiveTo investigate the changes of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to paraquat (PQ).
MethodsAdult healthy SD rats were randomly divided into a control group (n=8) and three experimental groups (PQ in low dosage of 15 mg/kg,medium dosage of 30 mg/kg,and high dosage of 60 mg/kg,n=24 in each group). The rats in three experimental groups were intragastrically administered with PQ,and the rats in the control group were treated with saline by gavage. Two rats in the control group and six rats in three experimental groups were sacrificed on 1st,7th,14th,and 21st day after exposure respectively. BALF was collected for measurement of interleukin-1(IL-1),IL-6,macrophage inflammatory protein-2(MIP-2),monocyte chemoattractant protein-1(MCP-1),and biopterin by ELISA.
ResultsThe levels of cytokines in all experimental groups were higher than those in the control group at any time point. In the exposure day 1 to day 14, IL-1 and biopterin levels in BALF increased significantly with the increase in PQ dose. On 14th and 21st day,IL-6 level in BALF increased significantly with the increase in PQ dosage. The levels of IL-1,IL-6,and biopterin in the experimental groups reached the peak on 14th day. On 14th day,the MIP-2 level in BALF of high-dosage group was significantly higher than that of low-dosage and medium-dosage groups (all P<0.05). The level of MCP-1 in the low-dosage group was lower than that in the medium-dosage and high-dosage groups at any time point (P<0.05).
ConclusionIL-1,IL-6,MIP-2,MCP-1,and biopterin may play important roles in the development and progression of PQ-induce lung inflammation.
