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目的 :观察有机氯杀虫剂dieldrin对培养的PC12细胞增殖及对其酪氨酸羟化酶mRNA(THmRNA)表达的影响 ,探讨该毒物致帕金森病 (PD)的可能机制。方法 :以MPP+ 为阳性对照 ,用不同浓度 (10 -4 ～ 1mmol·L-1)的MPP+ 和dieldrin分别于预PC12细胞 2 4h后计细胞数 ,并采用半定量逆转录聚合酶链式反应 (RT PCR)方法测定THmRNA表达的改变。结果 :(1)MPP+ 和dieldrin对PC12细胞均有毒性 ,1mmol·L-1的MPP+ 可使细胞数减少至对照组的 45 % (P <0 0 1) ,低于此浓度的MPP+ 对细胞增殖无影响 ;但 0 1mmol·L-1的dieldrin就可使细胞数减少至对照组的 3 0 % (P <0 0 1) ,1mmol·L-1的dieldrin使PC12细胞全部死亡。 (2 )MPP+ 和dieldrin均可降低THmRNA的表达。 0 1mmol·L-1MPP+ 和dieldrin使细胞THmRNA的表达分别下降至对照组的 69 3 % (P >0 0 5 )和 61 7% (P <0 0 1)。结论 :Dieldrin不仅具有与MPP+ 相同的抑制培养的PC12细胞的增殖及THmRNA表达的作用 ,而且其对细胞的毒性强于MPP+ ,提示dieldrin是一种潜在的致PD物质 ,其与PD的关系值得进一步研究
OBJECTIVE: To observe the effect of dieldrin, an organochlorine pesticide, on the proliferation of cultured PC12 cells and the expression of tyrosine hydroxylase mRNA (THmRNA), and to explore the possible mechanism of the drug induced Parkinson’s disease (PD). Methods: MPP + was used as a positive control, and the cell number was counted after preincubation with MPP + and dieldrin at different concentrations (10 -4 ~ 1 mmol·L -1) for 24 h. Semi-quantitative reverse transcriptase-polymerase chain reaction RT PCR) method to determine the change of THmRNA expression. Results: (1) Both MPP + and dieldrin were toxic to PC12 cells. The MPP + concentration of 1mmol·L-1 could reduce the number of cells to 45% of the control group (P <0.01) However, dieldrin decreased the cell number to 30% of the control group (P <0.01) with dieldrin of 0 1 mmol·L-1, and dieldrin of 1 mmol·L-1 completely died of PC12 cells. (2) Both MPP + and dieldrin can reduce the expression of TH mRNA. 0 1 mmol·L-1MPP + and dieldrin decreased the expression of TH mRNA to 69 3% (P 0 05) and 61 7% (P 0 01) of the control group respectively. CONCLUSION: Dieldrin not only has the same effect as MPP + in inhibiting proliferation and TH mRNA expression in cultured PC12 cells, but also is more toxic to cells than MPP +, suggesting that dieldrin is a potential PD-induced substance and its relationship with PD is worth further the study