| Objectives: Long time cerebral hypoperfusion can lead to excessive oxidative stress in many organs,which plays an important role in the process of neuronal damage and cognitive dysfunction.Heme oxygenase(HO)is the key enzyme and the rate-limiting enzyme in the decomposition of heme metabolism,and it is also an important endogenous antioxidant system,which has remarkable anti-oxidative stress ability.In the present study,the old SD rats with chronic cerebral hypoperfusion models were set up,and the expression of HO-1 and HO-2,which were key elements of HO family were detected,and their roles and significance were explored in the liver tissues.Methods: The old SD rat models with cerebral hypoperfusion were established by permanent bilateral common carotid artery occlusion(2VO).The cortical blood flow was detected.Hematoxylin eosin staining was used for observing the morphological changes of the rats' liver cells.Serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured in the blood samples collected from inferior vena cava? The activity of HO in the liver tissues was detected by ELISA.The location and expression of HO-1 and HO-2 was determined by immunohistochemical(IHC)staining.Finally,the expression of HO-1 and HO-2 at mRNA and protein levels were detected by RT-PCR and Western blot,respectively.Results: Compared with the sham-operated group,on the 7th d after 2VO operation,the area ratio of cortical blood flow was significantly decreased,and it reached the lowest value;at 14 d,21 dafter 2 VO,the area ratio of cortical cerebral blood flow was gradually increased,and at 28 d,it recovered to the normal level.The HE staining results showed that compared with sham operated group,on the first day after 2VO,the liver cells had hydropic degeneration due to ischemia,manifested with increased cell volume,transparent cytoplasm;and on the seventh day after 2VO,the hydropic degeneration was the most significant;after 14,21,28 days,liver cells vacuslation has improved,but has not yet recovered to the normal level.Liver function test results showed thatALT and AST were significantly increased 7 d after 2VO,and the difference was statistically significant(P<0.01),but they were still in normal range,there was no clinical significance;and with the extension of time,the concentration of ALT and AST were gradually decreased,28 d after operation,they were both recovered to normal level.IHC,RT-PCR and Western blot has showed that,compared with the sham operated group,the expression of HO-1 was rapidly increased on the first day after 2VO,and on the seventh day,it reached a peak(p<0.01),which was consistent with the changes of HO activity in the livers.Nevertheless,the changes of HO-2 in the liver tissues were not significant.Conclusion: Chronic cerebral hypoperfusion can lead to the slight damage of the morphological structure of liver cells,but the functions of liver is in normal?status,all of which is tightly related with the dynamic changes of HO-1 and heme oxygenase activity,and they suggest that HO-1 may play a protective role in the liver tissue of chronic cerebral hypoperfusion. |
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