Qiu Qiao-meng, Liu Yao, Song Qin, Ge Yun, Hong Guang-liang, Lu Zhong-qiu, Liang Huan, Li Meng-fang
Emergercy Medical Department, The First Affiliated Hospital, Wenzhou Medical College, Zhejiang Province, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012 Feb;30(2):89-96.
To observe the effects of hemoperfusion on oxidative stress status and the levels of matrix metallo proteinase (MMP-2, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) in lungs, livers and kidneys in paraquat poisoning rabbits, and to explore the mechanism of therapeutic effects induced by HP on acute paraquat poisoning.
Seventy eight rabbits were randomly divided into normal control group (N group, n=6), exposure groups (PQ group, n=24), hemoperfusion treatment group (HP treatment group, n= 24) and blank control group (HP group, n=24). The PQ, HPQ and HP groups were divided into 4 observation time groups (1, 3, 7 and 21 d). N group was exposed to 5 ml normal saline and PQ group was exposed to 50 mg/kg PQ by oral gavage. In 1 h after PQ exposure, HPQ group was exposed to the activated carbon hemoperfusion for 2 h. The content or activity of MDA, SOD and GSH-Px in lungs, livers and kidneys were detected, the expression levels of MMP-2, MMP-9 and TIMP-1 were measured with immunohistochemical SP method for all groups.
The contents of MDA in lungs, livers and kidneys of PQ and HPQ groups decreased and the activities of SOD and GSH-Px in lungs, livers and kidneys of PQ and HPQ groups increased with observation time. The expression levels of MMP-2, MMP-9 and TIMP-1 in PQ and HPQ groups enhanced on the first day, PQ group was most obvious. Along with the observation time extended, all kinds of positive expression were still high. Compared with normal control group, the activities of serum SOD and GSH-Px in PQ and HPQ groups declined significantly, but the contents of serum MDA increased; the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues increased obviously, the ration between MMP-9 and TIMP-1 significantly increased (P < 0.05). Compared with PQ group, the activities of SOD and GSH-Px in HPQ group significantly increased, the content of MDA declined, the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues declined obviously, the ration between MMP-9 and TIMP-1 significantly declined, but higher than N group, the differences were statistically significant (P < 0.05).
The oxidative stress and MMPs may be involved in the pathogenesis of tissue injuries induced by paraquat. The treatment with HP could obviously reduce oxidative stress and the expression levels of MMP-2, MMP-9 and TIMP-1, enhance the ration between MMP-9 and TIMP-1. So HP treatment could play a role in rescuing the PQ poisoning and protecting the organs function.
观察血液灌流对百草枯中毒兔肺、肝、肾组织氧化应激状态及基质金属蛋白酶（MMP-2、MMP-9）、金属蛋白酶组织抑制剂（TIMP-1）水平的影响，探讨血液灌流对急性百草枯中毒的治疗作用机制。
将78只兔随机分为正常对照组（N组，n=6）、染毒组（PQ组，n=24）、血液灌流治疗组（HP治疗组，n=24）和空白对照组（HP组，n=24）。PQ组、HPQ组和HP组再分为4个观察时间组（1、3、7和21 d）。N组经口灌胃5 ml生理盐水，PQ组经口灌胃50 mg/kg百草枯。PQ染毒后1 h，HPQ组行活性炭血液灌流2 h。检测各组肺、肝、肾组织中丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性，采用免疫组织化学SP法检测各组MMP-2、MMP-9和TIMP-1的表达水平。
PQ组和HPQ组肺、肝、肾组织MDA含量随观察时间延长而降低，SOD、GSH-Px活性随观察时间延长而升高。PQ组和HPQ组MMP-2、MMP-9和TIMP-1表达水平于第1天升高，PQ组最为明显。随着观察时间延长，各种阳性表达仍处于较高水平。与正常对照组比较，PQ组和HPQ组血清SOD、GSH-Px活性明显降低，血清MDA含量升高；肺、肝、肾组织MMP-2、MMP-9和TIMP-1表达水平明显升高，MMP-9与TIMP-1比值显著升高（P<0.05）。与PQ组比较，HPQ组SOD、GSH-Px活性明显升高，MDA含量降低，肺、肝、肾组织MMP-2、MMP-9和TIMP-1表达水平明显降低，MMP-9与TIMP-1比值显著降低，但高于N组，差异有统计学意义（P<0.05）。
氧化应激及基质金属蛋白酶可能参与百草枯所致组织损伤的发病机制。血液灌流治疗可明显减轻氧化应激，降低MMP-2、MMP-9和TIMP-1表达水平，提高MMP-9与TIMP-1比值，对百草枯中毒起到救治及保护脏器功能的作用。
