Role of Rac1 in cerebral ischemia-reperfusion injury in diabetic rats: the relationship with mitopaghy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of Rac1 in cerebral ischemia-reperfusion (I/R) injury and the relationship with mitopaghy in diabetic rats.Methods:SPF healthy adult male Sprague-Dawley rats, aged 8 weeks, weighing 250-280 g, in which diabetes mellitus was induced by intraperitoneal streptozotocin, were used in this study.Forty-eight rats with diabetes mellitus were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (sham group), cerebral I/R group (I/R group), I/R plus lentivirus inhibiting Rac1 group (I/R+ shRac1 group), and I/R plus lentivirus-negative control group (I/R+ NC group). Cerebral I/R was induced by 90-min middle cerebral artery occlusion followed by 24-h reperfusion.In I/R+ shRac1 and I/R+ NC groups, Rac1 shRNA lentivirus vector and lentivirus negative control vector 10 μl were injected via the right lateral cerebral ventricle at 7 days before establishing the model, respectively.Rats were sacrificed at 24 h of reperfusion, and brains were removed for determination of cerebral infarct size, expression of BNIP3, P62, LC3Ⅰ and LC3Ⅱ (by Western blot). The LC3Ⅱ/LC3 Ⅰ ratio was calculated. Results:Compared with sham group, the cerebral infarct size was significantly increased in the other three groups ( P<0.05). Compared with I/R group, the cerebral infarct size was significantly decreased, LC3Ⅱ/LC3Ⅰratio was increased, the expression of BNIP3 was up-regulated, and the expression of P62 was down-regulated in group I/R+ shRac1 ( P<0.05 or 0.01), and no significant change was found in each index in group I/R+ NC ( P>0.05). Compared with I/R+ NC group, the cerebral infarct size was significantly decreased, LC3Ⅱ/LC3Ⅰratio was increased, the expression of BNIP3 was up-regulated, and the expression of P62 was down-regulated in group I/R+ shRac1 ( P<0.05 or 0.01). Conclusion:The mechanism by which Rac1 reduces cerebral I/R injury is related to enhancing mitophagy in diabetic rats.