Mechanism of protection of 3-hydroxy-olea-12-en-28-oic acid in early brain injury of rat models after subarachnoid hemorrhage / 中华神经医学杂志

ABSTRACT

Objective:To discuss the antioxidant and anti-apoptosis effects of 3-hydroxy-olea- 12-en-28-oic acid (OA) on subarachnoid hemorrhage (SAH) and their mechanisms in rat models.Methods:In experiment one: 144 SD rats were divided into sham-operated group, SAH group and SAH+20 mg/kg OA group by random number table method ( n=48); SAH models were established by standard endovascular puncture method; rats in the SAH+20 mg/kg OA group received intraperitoneal injection of OA one h after modeling, while rats in the sham-operated group received the same operation without perforation; brain edema, destruction of blood-brain barrier, SAH severity degrees (Sugawa scale scores), neurological function scale scores and other early brain injury-related indicators were detected in rats from the three groups; the levels of malondialdehyde (MDA), superoxide dismutase (SOD) were investigated; the activation of nuclear factor related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis and neuronal apoptosis after SAH were detected. In experiment two: another 36 rats were divided into sham-operated group, SAH model group, sham operated+negative control siRNA group, SAH+negative control siRNA group, sham operated+Nrf siRNA group and SAH+Nrf siRNA group according to random number table method ( n=6); treatment methods in the sham-operated group and SAH modeling methods were the same as experiment one; negative control siRNA or Nrf siRNA were injected into the lateral ventricle of rats in the later 4 groups 24 h before SAH modeling; expressions of apoptosis-related factors in the downstream of Nrf2/HO-1 axis were detected in rats from the 6 groups. Results:In experiment one: (1) as compared with rats in the SAH group, rats in the SAH+20 mg/kg OA group had significantly decreased Sugawa scale scores, statistically increased neurological function scale scores and balance beam scale scores, significantly decreased brain moisture content and Evans blue exhalation rate ( P<0.05); (2) as compared with SAH group, SAH+20 mg/kg OA group had significantly decreased MDA level, and significantly increased SOD, glutathione peroxudase and catalase levels ( P<0.05); (3) the expressions of Nrf2, HO-1 and B-cell lymphoma-2(Bcl-2) were significantly increased, the expressions of apoptosis-related factors cytochrome-C, caspase-3 and activated caspase 3 were signficantly decreased, and the number of apoptotic neurons was significantly samller in the SAH+20 mg/kg OA group as compared with those in the SAH group ( P<0.05). In experiment two: as compared with those in the SAH+negative control siRNA group, the protein expressions of HO-1 and Bcl-2 in the SAH+Nrf siRNA group were significantly decreased, while the expression levels of cytochrome C, caspase-3 and activated caspase 3 were statistically increased ( P<0.05). Conclusion:OA can reduce the occurrence of oxidative stress and neuronal apoptosis by activating Nrf2/HO-1 axis.