活化PPAR-γ对特发性血小板减少性紫癜小鼠NOS的影响

Effect of activited PPAR-γ on the generation of NOS in idiopathic thrombocytopenic purpura(ITP) model mouse

目的探讨在特发性血小板减少性紫癜(ITP)模型小鼠体内,过氧化物酶体增生物激活受体γ(PPAR-γ)对一氧化氮合酶(NOS)生成的影响。方法 ITP模型小鼠分成罗格列酮试验组、GW9662对照组和磷酸盐缓冲液(PBS)对照组,罗格列酮试验组用相同浓度(20umol/L)的PPAR-γ激活剂噻唑烷二酮(thiazolidinediones,TZD)类药物罗格列酮进行灌肠,同时设立的GW9662对照组使用PPAR-γ特异性拮抗剂GW9662的终浓度为10μmol/L,PBS对照组使用相同体积的磷酸盐缓冲液进行灌肠,用药6、12、18、24和30h后,检测小鼠血清中NOS活性和血液淋巴细胞PPAR-γmRNA表达情况。结果血清中NOS在第6,12,18,24和30h的活性,罗格列酮试验组高于GW9662对照组及PBS对照组(P均<0.05)。在罗格列酮试验组中,NOS活性随着用药时间的延长而升高,各测量时间点NOS活性具有统计学差异(P<0.05),PPAR-γmRNA的表达随着时间的延长而增加(P<0.05),PPAR-γ的表达与NOS活性呈正相关(r=0.82,P<0.05)。结论在ITP小鼠模型内,PPAR-γ活化剂能够以时间依赖的形式增加NOS的活性,PPAR-γ可能通过NOS途径来发挥相应的生理功能。

Objective To investigate the impact and significance PPAR-γ on NOS production in idiopathic thrombocytopenic purpura（ITP）model mouse.Mehods ITP model mice were divided into rosiglitazone experimental group,GW9662 control group and phosphate buffered saline（PBS）control group.The mice in rosiglitazone experimental group were given with the same concentration（20umol/L）of the PPAR-γ activator thiazolidine drug rosiglitazone for enema,at the same time,GW9662 control group were established by the use of PPAR-γ antagonist GW9662 with the final concentration of 10μM,while the mice in PBS control group were given the same volume of phosphate buffer.The NOS activities were determined 6,12,18,24 and 30 hours after the usage of drug and the expression of PPAR-γmRNA was determined in blood lymphocytes by RT-PCR.Results The NOS activity in mice of rosiglitazone experimental group was higher than the GW9662 control group and PBS control group in the first 6h,12h,18h,24h and 30h（all P0.05）.In rosiglitazone experimental group,NOS activities increased along with elongation of the duration of drug usage,showing significant differences（P0.05）and the expression of PPAR-γmRNA increased along with progressing of the time（P0.05） In addtition,the NOS activities and the expression of PPAR-γ expression were positively correlated（r=0.82,P0.05）.Conclusions PPAR-γ activator was able to increase NOS activities relying on the time of drug usage and PPAR-γ might adjust the target factors by NOS pathway in ITP model mouse.