论文部分内容阅读
目的:探讨百草枯(PQ)与lactacystin对黑质细胞的协同毒性作用。方法:取SD雄性大鼠56只,随机分为NS组、lactacystin组(以下简称lact组)、PQ组和双因素组,每组14只。PQ组和双因素组预先每日口服小剂量PQ 0.5 mg·kg-1,NS组和lact组每日口服等量的NS,连续喂养8周后,在lact组和双因素组大鼠单侧SNc立体定向注射低剂量蛋白酶体抑制剂lactacystin 2 μg,NS组和PQ组注射等量的NS。观察大鼠行为变化、TH阳性细胞数以及α-synuclein蛋白表达变化。结果:仅双因素组大鼠出现严重的动作迟缓、少动、姿势异常以及APO诱导的持续左向旋转;黑质部TH阳性细胞数较NS组显著减少,且大于lact组和PQ组两组减少之和(P< 0.05);双因素组黑质细胞α-synuclein的表达较NS组显著增高,多数细胞内出现α-synuclein免疫反应呈强阳性的Lewy小体。结论: lactacystin与PQ之间存在协同作用,长期小剂量PQ的暴露能显著增加蛋白酶体功能轻微损害的大鼠患PD的风险。
Objective: To investigate the synergistic toxicity of paraquat (PQ) and lactacystin on nigrocytic cells. METHODS: Fifty-six male SD rats were randomly divided into NS group, lactacystin group (hereinafter referred to as lact group), PQ group and two-factor group, 14 in each group. The PQ group and the two-factor group were pretreated with small doses of PQ 0.5 mg·kg-1 daily. The NS group and the lact group were orally given the same amount of NS daily. After 8 weeks of continuous feeding, they were unilaterally fed to the lactating group and the two-factor group. SNc stereotaxically injected low-dose progesterone inhibitor lactacystin 2 μg, NS group and PQ group were injected with the same amount of NS. Observed changes in rat behavior, TH positive cells, and changes in the expression of α-synuclein protein. RESULTS: In the two-factor group, only rats exhibited severe bradykinesia, hypokinesia, and abnormal posture, as well as APO-induced sustained leftward rotation. The number of TH-positive cells in the substantia nigra decreased significantly compared with the NS group and was greater than that in the lact and PQ groups. The sum of the reduction (P<0.05); the expression of α-synuclein in the two-factor subgroup of nigrocytic cells was significantly higher than that of the NS group, and most of the cells exhibited a strong positive Lewy body of α-synuclein immunoreactivity. CONCLUSIONS: There is a synergistic effect between lactacystin and PQ, and long-term low-dose PQ exposure significantly increases the risk of PD in rats with mildly impaired proteasome function.