姜黄素对鱼藤酮诱导的黑质多巴胺能神经元损伤的保护作用

Protective Effect of Curcumin on Rotenone- induced Dopaminergic Neuron Injury in the Substantia Nigra

目的观察姜黄素对由鱼藤酮诱导的慢性帕金森病大鼠模型黑质多巴胺能神经元损伤的保护作用并探讨其可能机制。方法 2014年12月—2015年5月,选取清洁级雄性SD大鼠80只按随机区组法分为溶剂对照组、姜黄素组、鱼藤酮组、治疗组,每组20只。采用脑切片免疫组化染色法检测大鼠脑黑质区酪氨酸羟化酶(TH)阳性细胞数,Western blotting法检测大鼠脑黑质区沉默信息调节因子3(SIRT3)、P47phox表达水平,流式细胞仪检测大鼠脑黑质区活性氧(ROS)水平。结果 4组大鼠脑黑质区TH阳性细胞数比较,差异有统计学意义(P<0.05)。鱼藤酮组大鼠脑黑质区TH阳性细胞数低于溶剂对照组、姜黄素组(P<0.05);治疗组大鼠脑黑质区TH阳性细胞数低于溶剂对照组、姜黄素组,高于鱼藤酮组(P<0.05)。4组大鼠脑黑质区SIRT3、P47phox表达水平比较,差异均有统计学意义(P<0.05)。鱼藤酮组脑黑质区SIRT3表达水平低于溶剂对照组、姜黄素组(P<0.05);治疗组脑黑质区SIRT3表达水平低于溶剂对照组、姜黄素组,高于鱼藤酮组(P<0.05)。鱼藤酮组脑黑质区P47phox表达水平高于溶剂对照组、姜黄素组(P<0.05);治疗组脑黑质区P47phox表达水平高于溶剂对照组、姜黄素组,低于鱼藤酮组(P<0.05)。4组大鼠脑黑质区ROS水平比较,差异有统计学意义(P<0.05)。鱼藤酮组大鼠脑黑质区ROS水平高于溶剂对照组、姜黄素组(P<0.05);治疗组大鼠脑黑质区ROS水平高于溶剂对照组、姜黄素组,低于鱼藤酮组(P<0.05)。结论姜黄素可有效拮抗鱼藤酮诱导的慢性帕金森病大鼠多巴胺能神经元损伤,其机制可能与姜黄素通过促进SIRT3的表达清除小胶质细胞源性ROS有关。

Objective To investigate the protective effect of curcumin on rotenone - induced dopaminergic neuron injury in the substantia nigra of model rats with chronic Parkinson disease（ PD）and it possible mechanism. Methods From December 2014 to May 2015,80 cleaned male SD rats were selected and randomly divided into solvent control group,curcumin group,rotenone group and treatment group,20 rats in each group. Brain section immuno - histochemical staining method was used to detect the number of positive cells of tyrosine hydroxylase（TH）in the substantia nigra. The expression levels of SIRT3 and P47phox in the substantia nigra were detected using Western blotting method,and reactive oxygen species（ ROS）in the substantia nigra was detected using flow cytometry. Results The four groups were significantly different in the number of TH positive cells in the substantia nigra（P 〈 0. 05）. Rotenone group was lower than solvent control group and curcumin group in the number of TH positive cells in the substantia nigra（ P 〈 0. 05）;treatment group was lower than solvent control group and curcumin group and was higher than rotenone group in the number of TH positive cells in the substantia nigra（P 〈 0. 05）. The four groups were significantly different in the expression levels of SIRT3 and P47phox in the substantia nigra（ P 〈 0. 05）. Rotenone group was lower than solvent control group and curcumin group in the expression level of SIRT3 in the substantia nigra＆amp;nbsp;（P 〈 0. 05）;treatment group was lower than solvent control group and curcumin group and higher than rotenone group in the expression level of SIRT3 in the substantia nigra（ P 〈 0. 05）. Rotenone group was higher than solvent control group and curcumin group in the expression level of P47phox in the substantia nigra（P 〈 0. 05）;treatment group was higher than solvent control group and curcumin group and lower than rotenone group in the expression level of P47phox in the substantia nigra（P 〈0. 05）. The four groups were significantly different in ROS level in the substantia nigra（P 〈 0. 05）. Rotenone group was higher than control group and curcumin group in ROS level in the substantia nigra（P 〈 0. 05）;treatment group was higher than solvent control group and curcumin group and lower than rotenone group in ROS level in the substantia nigra（P 〈 0. 05）. Conclusion Curcumin can effectively antagonize rotenone - induced dopaminergic neuron injury in rats with chronic PD,and the mechanism may be related with the obliteration of microglia - derived ROS by increasing the expression of SITR3.