神经酸对紫杉醇诱导的神经细胞PC-12损伤的保护机制  

The protective effects and mechanism of nervonic acid on paclitaxel treated PC-12 cells

作　　者：付婷婷 马柯 李嘉 周卫东 赵晓山[2,3] 王昌俊 谭为 

机构地区：[1]广东省人民医院(广东省医学科学院)中医科、广东省老年医学研究所中医科,广州510080 [2]南方医科大学中医药学院 [3]南方医科大学附属南方医院中医科 [4]江西省新余市人民医院

出　　处：《脑与神经疾病杂志》2017年第12期736-741,共6页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金资助项目(81302958,81373582);广东省中医药局建设中医药强省课题资助(20131102、20151019、20151018)

摘　　要：目的观察神经酸(NA)对紫杉醇(PTX)损伤的神经细胞活力、脂肪型脂肪酸结合蛋白(A-FABP)、神经丝蛋白(NF200)、p38及凋亡蛋白Bcl-2、Bax、Cyt C、活化的Caspase-3(cl-Caspase-3)和Bcl-2/Bax表达的影响。方法采用PTX处理PC-12细胞,检测PTX IC50浓度。MTS法检测不同浓度NA(5μmol·L^(-1)、10μmol·L^(-1)、20μmol·L^(-1))对PTX(IC50浓度)干预后的PC-12细胞的相对增殖率。原位缺口末端检测法(TUNEL法)检测DNA断裂情况。蛋白印迹法检测相关蛋白表达。结果 PTX促进正常PC-12细胞凋亡。NA对维持细胞形态,保持细胞活力有一定作用。TUNEL法显示,神经酸组绿色荧光明显少于紫杉醇组。与紫杉醇组相比,神经酸组a-FABP、p-p38、Cyt C、cl-Caspase3表达下调(P<0.01),NF200、Bcl-2表达上调(P<0.01),Bcl-2/Bax比值升高(P<0.01),p38、Bax无明显变化(P>0.05)。结论NA可减轻PTX诱导的神经细胞的凋亡损伤,其作用机制可能与上调NF200、Bcl-2、Bcl-2/Bax表达,下调a-FABP、p-p38、Cyt C、cl-Caspase3表达有关。Objective To investigate the protect effects of nervonic acid （ NA ） on paclitaxel （ PTX ） treated PC-12 cells, and observe the cell viability, the expressions of A-FABP, NF200, Bcl-2, Bax, CytC, cleaved caspase-3, and the Bcl-2/Bax expression ratio. Method The PC-12 cells were treated with 171~, and the ICS0 was measured by method of MTS. Then, MTS method was used to detect the relative proliferation rate of different concentrations （ 5 μmol L-1, 10 μmol L-1, 20 μmol L-1 ） of NA on PC-12 cells after treated with PTX （ IC50 ） intervention. Detect the DNA fragmentation by method of TUNEL. The expression of related proteins was detected by Western blotting. Results PTX promote PC-12 cells apoptosis. NA has a role in maintaining cell morphology and maintaining cell viability. The TUNEL method showed that the green fluorescence in nervonic acid group was significantly less than that in the paclitaxel group. Compared with the expression in paclitaxel group, the expression of a-FABP, p-p38, CytC and cl-caspase3 were down-regulated in nervonic acid group （ P〈0.01 ）, the NF200 and Bcl-2 were up-regulated （ P〈0.01 ）, the ratio of Bcl-2/Bax was increased （ P〈0.01 ） , and p38, Bax have no change （ P〉0.05 ） .Conclusion NA can reduce the PTX-induced injury on PC 12 cells. The mechanism may be related to the up-regulation of NF-200, Bcl-2, Bcl-2/Bax expression and down-regulation of a-FABP, p-p38, CytC and cl-Caspase3 expression.

关 键 词：神经酸 紫杉醇 凋亡 化疗 PC-12细胞 

分 类 号：R741[医药卫生—神经病学与精神病学]