铜锌超氧化物歧化酶和谷胱甘肽过氧化物酶1 mRNA表达及其酶活力与砷中毒肝损伤关系
Relationship between Arsenic Liver Injury and Transcriptional Expressions and Activities of Cu/ZnSuperoxide Dismutase and Glutathione Peroxidase 1 Enzymes
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摘要:
目的 了解燃煤砷暴露人群外周血中铜锌超氧化物歧化酶(Cu/Zn-SOD)和谷胱甘肽过氧化物酶(GSH-Px)1转录表达与酶活力的关系, 探讨其在燃煤型砷中毒肝损伤发生发展中的作用。 方法 选择燃煤型砷中毒病区 133例砷暴露者为砷暴露组(包括病区非病例组 25例和病例组 108例), 将病例组分为无明显肝病组(38例)和肝病组(分为轻度肝病组 43例和中重度肝病组 27例); 在非砷暴露村选择 34例经健康体检无异常的居民作为对照组。采集上述观察对象的外周血, 采用实时荧光定量 PCR法检测 Cu/Zn-SOD mRNA和 GSH-Px1 mRNA表达, 化学法检测 SOD、Cu/Zn-SOD和GSH-Px活力。 结果 与对照组比较, 肝病组 Cu/Zn-SOD mRNA和 GSH-Px1 mRNA表达量均明显升高(P < 0.05或 P < 0.01); 与病区非病例组比较, 肝病组 Cu/Zn-SOD mRNA表达量明显升高(P < 0.05); 各病例组间比较差异无统计学意义。与对照组和病区非病例组比较, 肝病组 SOD、Cu/Zn-SOD和 GSH-Px活力均明显降低(P < 0.05或 P < 0.01); 与无明显肝病组比较, 轻度肝病组 SOD和 Cu/Zn-SOD活力明显下降(P < 0.05), 而中重度肝病组三种酶活力均明显下降(P < 0.05或 P < 0.01); 与轻度肝病组比较, 中重度肝病组 SOD活力明显降低(P < 0.05)。Cu/Zn-SOD和 GSH-Px1转录表达与肝损伤程度呈正相关(P < 0.01), 酶活力与肝损伤程度呈负相关(P < 0.01), 且转录表达与其酶活力均呈负相关(P < 0.01)。 结论 砷可能通过调控 Cu/Zn-SOD和 GSH-Px1的转录表达水平而影响其酶活力, 参与砷中毒肝损伤的发生发展。 Abstract:Objective To analyze the correlation between the transcriptional expressions of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px)1 and their enzyme activities in peripheral blood of arsenic-exposed population from a coal-burning area, and to explore their effects on the development of liver injury in endemic arsenism caused by coal-burning. Methods The arsenic exposure group consisted of 133 people exposed to arsenic (including 25 non-cases and 108 cases) who were selected from the area with endemic arsenism caused by coal-burning. The case group was divided into no obvious hepatopathy group (38 cases) and 2 hepatopathy groups (including 43 mild and 27 moderate-severe cases). Another 34 normal persons from nonarsenic polluted villages were taken as the control group. Peripheral blood samples were collected from all subjects. The mRNA expressions of Cu/Zn-SOD and GSH-Px1 were detected by real-time quantitative reverse transcription polymerase chain reaction (qPCR). The activities of SOD, Cu/Zn-SOD and GSH-Px were detected by chemical methods. Results Compared with the control group, mRNA expressions of Cu/Zn-SOD and GSH-Px1 in the hepatopathy group were significantly higher (P < 0.05 or P < 0.01). Compared with the non-case group, Cu/Zn-SOD mRNA were significantly higher in the hepatopathy group (P < 0.05). There was no significant difference among case groups. Compared with the control group and the non-case group, activities of SOD, Cu/ZnSOD and GSH-Px decreased obviously in the hepatopathy group (P < 0.05 or P < 0.01). Compared with the no obvious hepatopathy group, activities of SOD and Cu/Zn-SOD significantly decreased in the mild hepatopathy group (P < 0.05), and activities of SOD, Cu/Zn-SOD and GSH-Px in the moderate-severe hepatopathy group significantly decreased (P < 0.05 or P < 0.01). Compared with the mild hepatopathy group, activities of SOD significantly decreased in the moderate-severe hepatopathy group (P < 0.05). Transcriptional expressions of Cu/Zn-SOD and GSH-Px1 were positively correlated with the degree of liver injury (P < 0.01); however, their activities were negatively correlated with the degree of liver injury (P < 0.01); and there were negative correlations between the transcriptional expressions and the activities of Cu/Zn-SOD and GSH-Px1. Conclusion The transcriptional expressions of Cu/Zn-SOD and GSH-Px1 may respectively influence their enzyme activities in arsenism; and a lower level of such enzymes may participate in the development of arsenic liver injury.
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