15-脱氧前列腺J2对糖尿病脑缺血再灌注损伤大鼠脑梗死体积及核转录因子-κb的影响

Effect of 15-deoxy-delta(12,14)-prostaglandin J2 on cerebral infarction volume and nuclear factorkappaB level in diabetic rat with acute cerebral ischemia reperfusion

目的观察15-脱氧前列腺J2(15d-PGJ2)对糖尿病脑缺血再灌注大鼠脑梗死体积及核转录因子-κb(NF-κb)的影响。方法将80只成年SD大鼠随机分为假手术组、正常血糖组、糖尿病组及15d-PGJ2干预组,每组20只。采用链脲佐菌素诱导糖尿病,应用改良的Zea-Longa法制作大鼠大脑中动脉缺血再灌注模型。15d-PGJ2干预组在成功制备糖尿病大鼠模型后,给予15d-PGJ2 200μg/kg·d腹腔注射21 d后制作大脑中动脉缺血再灌注模型。再灌注后3 h腹腔注射15d-PGJ2 400μg/kg,以后给予15d-PGJ2 200μg/kg·d腹腔注射,连续6 d。分别于再灌注24 h及7 d对各组大鼠进行神经功能评价,TTC染色计算脑梗死体积,常规HE染色观察组织形态变化;采用ELISA法检测NF-κb水平。结果与假手术组比较,正常血糖组、糖尿病组、15d-PGJ2干预组再灌注24 h及7 d的神经功能评分及NF-κb水平显著升高,梗死体积均显著增加(均P<0.05)。与糖尿病组比较,正常血糖组再灌注24 h及7 d的神经功能评分、NF-κb水平及脑梗死体积均显著降低(均P<0.05)。15d-PGJ2干预组大鼠再灌注24 h及7 d的神经功能评分、NF-κb水平及脑梗死体积显著低于糖尿病组及正常血糖组(均P<0.05)。结论高血糖可加重缺血及再灌注后的脑损伤。15d-PGJ2可以减轻糖尿病及脑缺血对大脑的损伤,改善神经功能,减少脑梗死体积及NF-κb含量。

Objective To investigate the effect of 15-deoxy-delta（ 12,14）-prostaglandin J2（ 15d-PGJ2） on cerebral infarction volume and nuclear transcription factor-kappa B（ NF-κb） level in diabetic rat with acute cerebral ischemia reperfusion. Methods Eighty adult SD rats were randomly divided into sham group,normal blood glucose group,diabetic group and 15d-PGJ2 intervention group,20 mice in each group. Diabetic model was builded by streptozotocin solution with intraperitoneal injection. Modified Zea-longa method was used to set up rat middle cerebral artery occlusion model after successful preparing diabetic rats. The 15d-PGJ2 intervention group received 15d-PGJ2200 μg/kg·d intraperitoneal injection in 21 d,then set up middle cerebral artery occlusion model with a modified Zea-longa method,3 h after reperfusion 15d-PGJ2 400 μg/kg·d intraperitoneal injection was given,and 15d-PGJ2200 μg/kg·d intraperitoneal injection was given in later 6 d. The neurological defitic scores were evaluated at 24 h,7 d after reperfusion,the cerebral infarction volume was calculated by TTC,and the change of tissue morphology was observed by HE staining. The level of NF-κb was evaluated by ELISA. Results Compared with sham group,the neurological defitic scores,the level of NF-κb and cerebral infarction volume in normal blood glucose group,diabetic group and 15d-PGJ2 intervention group at 24 h and 7 d after reperfusion were significantly increased（ all P 0. 05）.Compared with diabetic group,the neurological defitic scores,the level of NF-κb and cerebral infarction volume in normal blood glucose group were significantly decreased（ all P 0. 05）. The neurological defitic scores,the level of NF-κb and cerebral infarction volume in 15d-PGJ2 intervention group were significantly decreased than those in normal blood glucose group and diabetic group（ all P 0. 05）. Conclusions Hyperglycemia can exacerbates the brain damage after cerebral ischemia reperfusion. 15d-PGJ2 can reduce the brain damage of diabetes and cerebral ischemia,improve the nerve function,and reduce the cerebral infarction volume and NF-κb level.