叶黄素激活Nrf2/HO-1信号通路缓解2型糖尿病大鼠骨质疏松-现代医学

叶黄素激活Nrf2/HO-1信号通路缓解2型糖尿病大鼠骨质疏松

单位：1. 湖北中医药大学, 湖北武汉 430060;
2. 武汉市第五医院中医科, 湖北武汉 430060;
3. 武汉市第三医院中医科, 湖北武汉 430060

分类号：R589.5

出版年·卷·期（页码）：2023·51·第六期（834-840）

摘要：

目的：基于核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)信号通路探究叶黄素对2型糖尿病大鼠模型骨质疏松的保护机制研究。方法:68只大鼠随机分为假手术组和造模组，其中造模组大鼠通过腹腔注射链脲佐菌素(STZ)及切除双侧卵巢建立2型糖尿病性骨质疏松(T2DOP)大鼠模型，将造模成功的T2DOP大鼠随机分为T2DOP组、叶黄素组(200 mg·kg^-1叶黄素)、Nrf2抑制剂-ML385组(30 mg·kg^-1 ML385)、叶黄素+ML385组(200 mg·kg^-1叶黄素+30 mg·kg^-1 ML385)，每组10只。干预结束后，双能X射线检测大鼠骨密度(BMD)水平；试剂盒检测各组大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)及活性氧(ROS)水平；骨生物力学测量左侧股骨最大载荷、弹性模量和屈服载荷；HE检测右侧股骨组织形态学变化；蛋白免疫印迹(Western blotting)检测右侧股骨组织中Nrf2、HO-1蛋白表达水平。结果：与假手术组相比，T2DOP组SOD含量、BMD、最大载荷、弹性模量和屈服载荷、Nrf2、HO-1蛋白表达显著降低，MDA、ROS含量显著增加(P<0.05)；与T2DOP组相比，叶黄素组SOD含量、BMD、最大载荷、弹性模量和屈服载荷、Nrf2、HO-1蛋白表达显著增加，MDA、ROS含量显著降低，ML385组SOD含量、BMD、最大载荷、弹性模量和屈服载荷、Nrf2、HO-1蛋白表达显著降低，MDA、ROS含量显著增加(P<0.05)；与叶黄素组相比，叶黄素+ML385组SOD含量、BMD、最大载荷、弹性模量和屈服载荷、Nrf2、HO-1蛋白表达显著降低，MDA、ROS含量显著增加(P<0.05)；与ML385组相比，叶黄素+ML385组SOD含量、BMD、最大载荷、弹性模量和屈服载荷、Nrf2、HO-1蛋白表达显著增加，MDA、ROS含量显著降低(P<0.05)。结论：叶黄素可通过激活Nrf2/HO-1信号通路减轻氧化应激损伤，缓解T2DOP症状，保护T2DOP大鼠。

Objective: To explore the protective mechanism of lutein on osteoporosis in rats with type 2 diabetes based on nuclear factor erythroid-derived factor 2-related factor(Nrf2)/heme oxygenase-1(HO-1) signal pathway. Methods: 68 rats were randomly divided into the sham operation group and the model group, the rats in the model group were injected intraperitoneally with streptozotocin(STZ) and ovariectomized to establish the model of type 2 diabetes induced osteoporosis(T2DOP). T2DOP rats with successfully constructed were randomly divided into T2DOP group, lutein group(200 mg·kg^-1 lutein), Nrf2 inhibitor ML385 group(30 mg·kg^-1 ML385), and lutein+ML385 group(200 mg·kg^-1 lutein+30 mg·kg^-1 ML385), with 10 rats in each group. After the intervention, the bone mineral density(BMD) was measured by dual energy X-ray.The levels of malondialdehyde(MDA), superoxide dismutase(SOD) and reactive oxygen species(ROS) in serum were detected with the kit.The maximum load, elastic modulus and yield load of the left femur were measured by bone biomechanics.The histomorphological changes of right femur were detected by HE.The expression of Nrf2 and HO-1 proteins in the right femur were detected by Western blotting. Results: Compared with sham operation group, the content of SOD, bone mineral density, maximum load, elastic modulus, yield load, the expression of Nrf2 and HO-1 proteins in T2DOP group were significantly decreased, the contents of MDA and ROS were significantly increased(P<0.05). Compared with T2DOP group, the content of SOD, bone mineral density, maximum load, elastic modulus, yield load, the expression of Nrf2 and HO-1 proteins in lutein group were significantly increased, the contents of MDA and ROS were significantly decreased; however, the content of SOD, bone mineral density, maximum load, elastic modulus, yield load, the expression of Nrf2 and HO-1 proteins in ML385 group were significantly decreased, the contents of MDA and ROS were significantly increased(P<0.05).Compared with lutein group, the content of SOD, bone mineral density, maximum load, elastic modulus, yield load, the expression of Nrf2 and HO-1 proteins in lutein+ML385 group were significantly decreased, the contents of MDA and ROS were significantly increased(P<0.05).Compared with ML385 group, the content of SOD, bone mineral density, maximum load, elastic modulus, yield load, the expression of Nrf2 and HO-1 proteins in lutein+ML385 group were significantly increased, the contents of MDA and ROS were significantly decreased(P<0.05). Conclusion: Lutein can alleviate oxidative stress injury, alleviate T2DOP symptoms and protect T2DOP rats by activating Nrf2/HO-1 signal pathway.

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