| Objective: To establish the OSAS rat model through CIH,and observe the behavioral changes,pathological morphological changes in the hippocampal CA1 and CA3 regions,the expression sites of TRPV1 in nerve cells and expression changes of TRPV1 in the OSAS rats treated with TRPV1 agonist Capsaicin and inhibitor AMG9810,and explore the role of TRPV1 in the cognitive dysfunction caused by OSAS rats.Methods: 64 male SD rats were randomly divided into normal control group,CIH 7d,CIH 14 d,CIH 21 d,CIH 28 d,Capsaicin intervention group(CIH 28d),AMG9810 intervention group(CIH 28d)and DMSO(dimethyl sulfoxide)solvent control group(CIH 28d).Except the normal group,the other experimental rats were placed in a cage and then placed in a hypoxic chamber.The oxygen concentration in the chamber was controlled to reach a hypoxic state by filling the hypoxic chamber with nitrogen to simulate the hypoxia-reoxygenation-hypoxia Characteristics OSAS rat model.After the successful models were built,Morris Water Maze was used to observe the behavioral changes and taken materials after the end.The Nissl stain method was used to observe the pathological morphology of hippocampus neurons,the location of positive stained cells in immunohistamorphosis to observe TRPV1,and the protein expression and change law of TRPV1 in the hippocampus region of each group of experimental rats were detected by Western blotting.The comparative observation gave Capsaicin and AMG9810 the effect of changes in TRPV1 expression in the hippocampus of OSAS model rats.Results:(1)During the establishment of the experimental model,the oxygen saturation monitor was used to detect the changes of the oxygen saturation in the tail of the rats during hypoxia and reoxygenation,and it was found that the average oxygen saturation of the rats during hypoxia(66.85±2.01)% was significantly lower than the average oxygen saturation of the rats during reoxygenation(96.98±1.38)%(P <0.05).With the prolongation of model establishment time,the experimental rats show symptoms such as holding back,restlessness,raising head and breathing.(2)Through Morris water maze test on the behavior of the rats after the establishment of the model,it was found that: compared with the CIH 7d group,the results of escape latency and space exploration passing through the platform were similar in the normal control group(P > 0.05).The comparison of CIH 14 d,CIH21d and CIH 28 d in the three groups of rats and the normal control group showed that,with the extension of hypoxia time,the evadation incubation period became more obvious(P <0.05),while the number of space exploration crossing the platform decreased(P <0.05).CIH 28 d and DMSO solvent control group(CIH 28d)had no significant difference in escape latency and space exploration crossing times between the two groups(P >0.05).The escape incubation period of rats in Capsaicin intervention group(CIH 28d)was significantly shorter than that in DMSO control group(CIH 28d)(P <0.05),and the number of space exploration crossing the platform increased(P <0.05).The escape incubation period of rats in the AMG9810 intervention group(CIH 28d)was significantly longer than that in the DMSO control group(CIH 28d)(P <0.05),and the number of space exploration crossing the platform was reduced(P <0.05).(3)Nissl stain that observed in the CA1 and CA3 regions of the hippocampus showed that:normal control group cell arranged densely populated and orderliness,cellular level clearly visible,nucleolus,rich can be seen in the cytoplasm is patchy or dotted nissl bodies;In the CIH 28 d group,the number of nerve cells decreased and their arrangement was irregular,including nuclear shrinkage,nuclear rupture,irregular cell morphological structure,widened intercellular space,and absence or reduction of intracytoplasmic ntensite.Compared with the CIH 28 d group,the nerve cell damage in the Capsaicin intervention group was slightly better,the intercellular space was reduced,the number of cells was increased,and the nuclear shrinkage and nuclear fragmentation were improved.However,the AMG9810 group(CIH 28d)suffered more severe damage than the CIH 28 d group,and the number of cells was significantly reduced,and the number of nissl bodies were reduced or even close to none.(4)Immunohistochemical results showed that TRPV1 was mainly expressed in the cytoplasm of nerve cells in the CA1 and CA3 regions of the hippocampus,and the positive staining cells were brown-yellow or yellow.(5)Western blotting showed that TRPV1 was expressed in hippocampal tissues of rats in each group.There was no significant difference in the expression of TRPV1 protein in the hippocampal tissues of the CIH 7d group compared with the normal control group(P >0.05),while the expression of the three histone proteins in the CIH 14 d group,the CIH 21 d group and the CIH 28 d group were all decreased compared with the normal control group(P <0.05),and the protein expression gradually decreased with the increase of intermittent hypoxia time from the CIH 14 d group(P < 0.05).Compared with DMSO group(CIH 28d),there was no significant change in hippocampal protein expression(P >0.05).Protein expression in Capsaicin intervention group(CIH 28d)was significantly higher than that in DMSO group(CIH 28d)(P <0.05).The protein expression of AMG9810 group(CIH 28d)was significantly lower than that of DMSO group(CIH 28d)(P <0.05).Conclusion: Transient receptor potential family vanilloid subtype 1 plays an important role in the occurrence of cognitive impairment in OSAS rats,its agonists can improve the learning and memory functions of OSAS rats,and its inhibitor can aggravate OSAS rats cognitive dysfunction,indicating that transient receptor potential family vanilloid subtype 1 plays a protective role in OSAS-induced cognitive dysfunction. |
PDF Full Text Request