没食子酸丙酯对醋酸铅诱导的 SD 大鼠氧化应激和肝毒性的保护作用。
Protective Effects of Salidroside on Lead Acetate-induced Oxidative Stress and Hepatotoxicity in Sprague-Dawley Rats.
机构信息
Chinese-German Joint Laboratory for Natural Product Research, College of Biological Science and Engineering, Shaanxi University of Technology, Chaoyang Road, Hantai District, Hanzhong, 723000, Shaanxi, China.
Vitamin D research institute, Shaanxi University of Technology, Chaoyang Road, Hantai District, Hanzhong, 723000, Shaanxi, China.
出版信息
Biol Trace Elem Res. 2019 Oct;191(2):426-434. doi: 10.1007/s12011-019-1635-8. Epub 2019 Jan 21.
Lead has heavy metal toxicity which endangers human and animal health. Salidroside (SDS) is a natural antioxidant that has extensive pharmacological usage. However, its protective effects on lead-induced oxidative stress and hepatotoxicity has not been reported. In this study, we established an animal model to evaluate the protective effects of SDS on chronic lead exposure induced oxidative stress and hepatotoxicity. Forty healthy Sprague-Dawley (SD) rats were assigned to control group (control, animals were provided with distilled water, n = 10); lead acetate-exposed group (PbAc, animals received lead acetate solution of 500 ppm for 60 days, n = 10); low dosage of SDS-treated group (PbAc-SDS-L, lead acetate exposed animals were given intragastric SDS 150 mg/kg body weight for 60 days, n = 10); and high dosage of SDS-treated group (PbAc-SDS-H, lead acetate exposed animals were given intragastric SDS 300 mg/kg body weight for 60 days, n = 10). The results showed that lead exposure caused a significant increase in serum ALP, AST, ALT, and TB (P < 0.01), and these were reversed after treatment with salidroside for 60 days. Compared to the control, the liver GSH, SOD, and GSH-Px were decreased significantly after lead acetate exposure (P < 0.01). However, after treatment with SDS for 60 days, those were dose-dependently reversed. Similarly, MDA was significantly increased in the PbAc group (P < 0.01), and it was significantly decreased in SDS treatment group. Moreover, SDS ameliorated lead-induced congestion and necrosis of hepatocytes. In addition, the RT-PCR and immunohistochemistry results revealed that the PbAc group showed a significant increase in the protein and mRNA of cytochrome P450 2E1 (CYP2E1) and NADPH oxidase 2 (NOX2) in rat liver. Treatment with SDS significantly reversed CYP2E1 and NOX2 expressions in the liver of lead-exposed rats. The results above indicated that SDS has obvious antioxidant activity; it can cure liver injury caused by lead acetate by inhibiting oxidative stress and increasing the antioxidant stress activity, thus improving the liver tissue structure.
铅具有重金属毒性，危害人类和动物健康。红景天苷（SDS）是一种天然抗氧化剂，具有广泛的药理学用途。然而，它对铅诱导的氧化应激和肝毒性的保护作用尚未得到报道。在这项研究中，我们建立了一种动物模型来评估 SDS 对慢性铅暴露诱导的氧化应激和肝毒性的保护作用。将 40 只健康的 Sprague-Dawley（SD）大鼠分为对照组（对照组，给予蒸馏水，n=10）；醋酸铅暴露组（PbAc，给予 500ppm 醋酸铅溶液 60 天，n=10）；低剂量 SDS 处理组（PbAc-SDS-L，给予醋酸铅暴露动物 150mg/kg 体重的 SDS 灌胃 60 天，n=10）；高剂量 SDS 处理组（PbAc-SDS-H，给予醋酸铅暴露动物 300mg/kg 体重的 SDS 灌胃 60 天，n=10）。结果表明，铅暴露导致血清 ALP、AST、ALT 和 TB 显著升高（P<0.01），而经过 60 天的 SDS 治疗后这些指标均得到逆转。与对照组相比，铅醋酸盐暴露后肝 GSH、SOD 和 GSH-Px 显著降低（P<0.01）。然而，经过 60 天的 SDS 治疗后，这些指标呈剂量依赖性逆转。同样，PbAc 组 MDA 显著升高（P<0.01），而在 SDS 处理组中 MDA 显著降低。此外，SDS 改善了铅诱导的肝细胞充血和坏死。此外，RT-PCR 和免疫组织化学结果表明，PbAc 组大鼠肝 CYP2E1（CYP2E1）和 NADPH 氧化酶 2（NOX2）的蛋白和 mRNA 表达显著增加。SDS 处理显著逆转了铅暴露大鼠肝中 CYP2E1 和 NOX2 的表达。上述结果表明，SDS 具有明显的抗氧化活性；它可以通过抑制氧化应激和增加抗氧化应激活性来治疗醋酸铅引起的肝损伤，从而改善肝组织结构。
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