Protective effect and mechanism of ursodeoxycholic acid on cerebral ischemia-reperfusion injury in rats#br#
YOU Meigui1 TIAN Hua1 ZENG Yun2#br#
1.Department of Pharmacology, Department of Basic Medicine, Xiamen Medical College, Fujian Province, Xiamen 361023, China;
2.Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Fujian Province, Xiamen 361023, China
Abstract：Objective To study the protective effect and mechanism of ursodeoxycholic acid (UDCA) on cerebral ischemia-reperfusion injury in rats. Methods Forty male SD rats were divided into sham operation group, middle cerebral artery occlusion (MCAO) group, UDCA 60 mg/kg group, and UDCA 120 mg/kg group according to random number table method, with ten rats in each group. Rats were given prophylactic medicine for three days. MCAO model was established by thread bolt method. Reperfusion was realized after blocking for 1.5 hours. Rats continued to be given medicine for five days and half hour at the last administration, the neurological function score of rat was evaluated by Longa’s standard, 2,3,5-triphenyltetrazolium chloride staining was used to calculate the volume of cerebral infarction in rats. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in cerebral ischemic tissues of rats were measured. The expressions of PI3K and p-AKT proteins in rat hippocampus were detected. Results The neurological function score of MCAO group was higher than that of sham operation group (P ＜ 0.01). The neurological function scores of UDCA 60 mg/kg group and UDCA 120 mg/kg group were lower than those of MCAO group (P ＜ 0.05). In sham operation group, all brain tissues were rose red, and no infarct lesions were found; the cerebral infarction area of MCAO group showed obvious pale infarct area. The percentage of cerebral infarction in MCAO group was higher than that in sham operation group (P ＜ 0.01). The percentages of cerebral infarction tissue in UDCA 60 and 120 mg/kg groups were lower than those in MCAO group (P ＜ 0.05). The content of SOD in MCAO group was lower than that in sham operation group, and the content of MDA in MCAO group was higher than that in sham operation group (P ＜ 0.01). The contents of SOD in UDCA 60 and 120 mg/kg groups were higher than those in MCAO group, and the contents of MDA in UDCA 120 mg/kg groups were lower than those in MCAO group (P ＜ 0.05). The expressions of PI3K and p-AKT protein in hippocampus of MCAO group were lower than those of sham operation group (P ＜ 0.05). The expressions of PI3K and p-AKT protein in UDCA 60 and 120 mg/kg groups were higher than those in MCAO group (P ＜ 0.05). Conclusion UDCA has effects on the cerebral ischemia-reperfusion injury in rats, and its mechanism may be related to improvement of brain oxidative stress, regulating the AKT signaling pathway.
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