CAJ | 학술논문

目的探讨四氢吡咯二硫代氨基甲酸酯(pyrrolidine Dithiocarbamate,PDTC)对百草枯(paraquat,PQ)致肺损伤大鼠转化生长因子β1(TGF-β1)、基质金属蛋白酶(MMP-2)和基质金属蛋白酶组织抑制剂(TIMP-1)表达的影响.方法 54只SD大鼠随机分为对照组(生理盐水组)、单纯染毒组(4个组)和干预组(4个组).除对照组外,各组均一次性灌胃PQ40mg/kg染毒,PDTC干预组在PQ染毒后立即一次性腹腔注射PDTC 120 mg/kg.在染毒后3、7、14、21 d各取1组动物,用反转录-聚合酶链反应(RT-PCR)法及荧光定量PCR法检测肺组织中TGF-β1、MMP-2和TIMP-1基因的表达,并观察肺组织病理改变.结果与对照组相比.染毒组大鼠血浆TGF-β1蛋白、肺组织TGF-β1、MMP-2mRNA表达随时问延长呈现先升高后降低趋势,差异有统计学意义(P<0.05或P<0.01),TIMP-1表达持续增高,差异有统计学意义(P<0.01).PDTC干预组3、14 d TGF-β1mRNA表达分别为0.54±0.08、0.72±0.04,7、14 dMMP-2 mRNA表达分别为1.62±0.50、1.97±0.34,7、21 d TIMP.1 mRNA表达分别为1.79±0.21、2.00±0.34,与单纯染毒组相比,均明显降低,差异有统计学意义(P<0.05或P<0.01).结论 PDTC对肺损伤大鼠不同时期肺组织中TGF-β1、MMP-2及TIMP-1的mRNA表达均有一定的下调作用,可能是通过减轻中毒早期炎症的损伤、调整MMPs/TIMPs间的平衡,从而延缓肺纤维化的进程.
목적 탐토사경필각이류대안기갑산지(pyrrolidine Dithiocarbamate,PDTC)대백초고(paraquat,PQ)치폐손상대서전화생장인자β1(TGF-β1)、기질금속단백매(MMP-2)화기질금속단백매조직억제제(TIMP-1)표체적영향.방법 54지SD대서수궤분위대조조(생리염수조)、단순염독조(4개조)화간예조(4개조).제대조조외,각조균일차성관위PQ40mg/kg염독,PDTC간예조재PQ염독후립즉일차성복강주사PDTC 120 mg/kg.재염독후3、7、14、21 d각취1조동물,용반전록-취합매련반응(RT-PCR)법급형광정량PCR법검측폐조직중TGF-β1、MMP-2화TIMP-1기인적표체,병관찰폐조직병리개변.결과 여대조조상비.염독조대서혈장TGF-β1단백、폐조직TGF-β1、MMP-2mRNA표체수시문연장정현선승고후강저추세,차이유통계학의의(P<0.05혹P<0.01),TIMP-1표체지속증고,차이유통계학의의(P<0.01).PDTC간예조3、14 d TGF-β1mRNA표체분별위0.54±0.08、0.72±0.04,7、14 dMMP-2 mRNA표체분별위1.62±0.50、1.97±0.34,7、21 d TIMP.1 mRNA표체분별위1.79±0.21、2.00±0.34,여단순염독조상비,균명현강저,차이유통계학의의(P<0.05혹P<0.01).결론 PDTC대폐손상대서불동시기폐조직중TGF-β1、MMP-2급TIMP-1적mRNA표체균유일정적하조작용,가능시통과감경중독조기염증적손상、조정MMPs/TIMPs간적평형,종이연완폐섬유화적진정.
Objective To investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expres sion of transforming growth factor β1(TGF-β1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ). Methods Fifty-four healthy male SD rats were randomly assigned into the control group(normal saline), the PQ-treatment groups(4 groups)and the PDTC treatment groups (4 groups). Except the rats in the control group,the rats in the PQ group were garaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC(i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-β1 protein in the plasma, the mRNA expression of TGF-β1,MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR,while pathological changes of lung were examined under optical microscope and electrical microscope. Results The TGF-β1 protein,TGF-β1 and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P<0.05 or P<0.01),while the mRNA level of TIMP-1 was augmented continuously (P<0.01) throughout the study compared to the control group. In comparison with the PQ group,in the PDTC treatment group,the TGF-β1 mRNA expression on the 3rd and the 14th day,0.54±0.08 and 0.72±0.04 respectively,the MMP-2 mRNA expression on the 7th and 14th day, 1.62±0.50 and 1.97±0.34 respectively,and the TIMP-1 mRNA on the 7th and 21st day, 1.79±0.21 and 2.00±0.34 respectively,were significantly decreased (P<0.05 or P<0.01 ). Conclusion PDTC could attenuate paraquat-induced up-regulation of TGF-β1 and its mRNA expression, MMP-2 and TIMP-1 mRNA levels,which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjusting the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.