Effect Of HIF1α On The Injury Of Cognition In Rats With Chronic Cerebral Hypoperfusion

Objective To observe the impact of HIF-la on cognition in chronic cerebral hypoperfusion, we used the technology to synthetize lentivirus-mediated the HIF-lashRNA carrier decreased the level of expression of HIF-la in rat brain specifically.Methods We built three kinds of HIF-lashRNA, used lentivirus to package them. After measuring the virus titer, we used the rat glioma cells to identify the effective interference sequence. All the rats were randomly divided into sham-operated+injection of physiological saline (sham) group, bilateral carotid artery ligation+injection of physiological saline (2VO) group, bilateral carotid artery ligation+injection of empty vector (2VO+RNAi empty) group and bilateral carotid artery ligation+injection of HIF-lashRNA (2VO+RNAi) group. Object recognition test, Morris water maze, fluorescence real-time quantitative PCR, Western-blot and frozen sections were used to detect the cognition,the protein expression level of HIF-la, CREB, p-CREB, PSD95, MAP-2, SYN.Results Compared to sham rats, the ability of2VO rats to identify new objects was reduced. The escape latencies of2VO was extended. The fluorescence real-time quantitative PCR showed the level of HIF-la in2VO+RNAi group was lower than2VO+RNAi empty group. Western blot showed that the expression of HIF-1α in2VO group rats was increased. Compared to the2VO+RNAi empty group, the protein expression level of HIF-1α,CREB, p-CREB, MAP-2were reduced in2VO+RNAi group. The level of PSD95, SYN expression was almost same between the2VO+RNAi group and2VO+RNAi empty.Conclusion The chronic cerebral hypoperfusion in rats can cause cognitive impairment. By using RNAi to inhibit the HIF-la in the brain of rats, the cognition can be injured. HIF-la may be involved in the regulation of chronic cerebral hypoperfusion on cognition.