PPARγ激动剂吡格列酮对大鼠局灶性脑缺血再灌注损伤后JAK2/STAT3信号转导通路的影响

The influence of PPARγ agonists pioglitazone on focal cerebral ischemia-reperfusion injury and JAK2/STAT3 signal transduction pathway

目的观察过氧化物酶体增殖物激活型受体γ(peroxisome proliferators activated receptor gamma,PPARγ)激动剂吡格列酮对大鼠局灶性脑缺血再灌注损伤的保护作用及其对大鼠内源性酪氨酸激酶2(janus kinase2,JAK2)/信号转导子和转录激活子3(signal transducer and activator of transcription 3,STAT3)信号转导通路的影响,并对其作用机制进行探讨。方法采用改良线栓法制备大鼠局灶性脑缺血再灌注损伤模型。分为假手术组、缺血再灌注组、生理盐水干预组、吡格列酮干预组。分别采用神经功能评分法观察大鼠行为学评分的变化,HE染色观察大鼠脑组织损伤情况变化,western-blotting观察大鼠缺血半暗带区P-JAK2、P-STAT3表达的改变。结果PPARγ激动剂能够减少缺血再灌注损伤大鼠行为学评分,假手术组:0,模型组:(2.3±0.98),生理盐水干预组:(2.4±0.99),吡格列酮15 mg/kg组:(1.5±0.69)(P<0.05);减轻脑细胞坏死程度;降低缺血半暗带区P-JAK2、P-STAT3的表达,两种蛋白分别为假手术组:0、0,模型组:(0.89±0.06)、(0.27±0.03),生理盐水干预组:(0.88±0.05)、(0.28±0.04),吡格列酮15 mg/kg组:(0.23±0.04)、(0.10±0.02)(P<0.05)。结论PPARγ激动剂对大鼠脑缺血再灌注损伤具有保护作用,其作用机制与下调JAK2/STAT3信号转导通路有关。

Objective To investigate the protective effects of peroxisome proliferators activated receptor gam- ma agonist pioglitazone aganist rat focal cerebral ischemia-reperfusion injury and its effect on endogenous janus kinase 2 / signal transducer and activator of transcription 3signaling pathway and discuss its possible mechanism. Methods Experimental animals were divided into sham group, ischemia-reperfusion group, saline intervention group, pioglita- zone intervention group. Focal brain artery ischemia and reperfusion rats model was established using the modified suture method. Neurological function scores were used to assess the behavior. HE staining and Western-blotting were used to examine brain tissue injury, and expression levels of the P-JAK2 and P-STAT3 in cerebral ischemic penum- bra area, respectively. Results The neurological scores were 0 in sham group, 2.3 ± 0.98 in saline group, and 2.4 ± 0.99 in pioglitazone group, respectively. PPARy agonists sginficantly improved functional recvoery in ischemic rats compared with either saline or sham groups （P 〈 0.05） ; The expression levels of P-JAK2 and P-STAT3 were 0 and 0 in sham group, 0.89 ±0.06 and 0.27 ±0.03, in saline group and 0.23 ± 0.04 and 0.10 ± 0.02 in pioglitazone group, respectively. PPARγ agonists significantly reduced the expression levels of P-JAK2 and P-STAT3 （P 〈 0.05）. Conclusions PPARγ agonists can protect against cerebral ischemia-reperfusion injury probably through reduction of JAK2/STAT3 signal transduction pathway.