伐仑克林靶向α-syn蛋白对帕金森病大鼠的机制研究

目的研究伐仑克林靶向α-syn蛋白对帕金森病(PD)大鼠的机制。方法选取SPF级30只SD健康大鼠,将30只大鼠随机分为空白组、模型组、用药组各10只,模型组和用药组建立PD大鼠模型。建模成功后,用药组使用1mg·kg-1的伐仑克林灌胃,空白组和模型组不做任何处理。在大鼠给药1w后对三组大鼠行为学、线粒体活性(State3、State4、RCR)、α-syn(α-突触核蛋白)、LPO(过氧化脂)、MDA(丙二醛)水平及对大脑组织中Beclin1、LC3B、APP合成酶活力、p-mTOR、IRE1α、ASK1、P-JNK蛋白表达量进行检测。结果模型组大鼠悬尾静止时间、IRE1α、ASK1、P-JNK蛋白表达量、α-syn、LPO、MDA水平均高于空白组,且糖水测试、Beclin1、LC3B蛋白表达量、线粒体活性、APP合成酶活力、p-mTOR均低于空白组,(P<0.05);用药组大鼠悬尾静止时间、IRE1α、ASK1、P-JNK蛋白表达量、α-syn、LPO、MDA水平均高于空白组,且糖水测试、Beclin1、LC3B蛋白表达量、线粒体活性、APP合成酶活力、p-mTOR均低于空白组,(P<0.05);用药组大鼠悬尾静止时间、IRE1α、ASK1、P-JNK蛋白表达量、α-syn、LPO、MDA水平均低于模型组,且糖水测试、Beclin1、LC3B蛋白表达量、线粒体活性、APP合成酶活力、p-mTOR均高于模型组(P<0.05)。结论伐仑克林通过靶向α-syn蛋白,作用于其线粒体功能及内质网应激机制,提高其行为学能力,效果显著。

Mechanism of valencline targeting alpha-syn protein on Parkinson's disease rats

Objective To study the effect and mechanism of valencline targeting alpha-syn(α-syn) protein on Parkinson’s disease(PD) rats. Methods Thirty healthy SD rats of SPF grade were selected and randomly divided into blank group, model group and medication group with 10 rats each. PD rat model was established in model group and medication group. After successful modeling, the medication group was given 1 mg·kg-1 varenicline by gavage, while the blank group and the model group did not receive any treatment. Behavior,(α-syn), LPO(lipid peroxide), MDA(malondialdehyde), Beclin 1, LC3B, mitochondrial activity(State3, State4, RCR), APP synthase activity, p-mTOR, IRE1 alpha, ASK1 and P-JNK protein expression in brain tissues of three groups of rats were detected one week after administration. Results The tail suspension rest time, IRE1 alpha, ASK1, P-JNK protein expression, α-syn, LPO and MDA levels of model group rats were higher than those of blank group, and the expression of sugar water test, Beclin 1, LC3 B protein, mitochondrial activity, APP synthase activity and p-mTOR of model group rats were lower than those of blank group, with statistical difference(P<0.05). The levels of stop time, IRE1 alpha, ASK1, P-JNK protein expression, α-syn, LPO and MDA were higher than those of the blank group, and the levels of sugar test, Beclin 1, LC3 B protein expression, mitochondrial activity, APP synthase activity and p-mTOR were lower than those of the blank group, with statistical differences(P<0.05). The levels of P-JNK protein, alpha-syn, LPO and MDA in the model group were lower than those in the model group, and the levels of sugar water test, Beclin 1, LC3B protein expression, mitochondrial activity, APP synthase activity and p-mTOR in the model group were higher than those in the model group, with statistical differences(P<0.05).Conclusion Valencine can improve its behavioral ability by targeting α-syn protein and acting on its mitochondrial function and endoplasmic reticulum stress response.