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1.
Chinese Journal of Pathophysiology ; (12): 845-856, 2018.
Article in Chinese | WPRIM | ID: wpr-701205

ABSTRACT

AIM:To evaluate the role of heat shock protein 22(HSP22)in atherosclerosis(AS)induced by high-fat diet and in the intervention with atorvastatin(Ator).METHODS: Total 3 groups of 8 ~9-week-old ApoE-/-, HSP22-/-ApoE-/-and HSP22 +ApoE-/-male mice were used,with 18 mice in each group.After 1 week of adaptive feeding, the mice in each group were randomly divided into 2 subgroups: control group, and Ator group, HSP22 knockout group (KO group)and HSP22 knockout with Ator treatment group(KO+Ator group),and HSP22 overexpression group(Tg group)and HSP22 overexpression with Ator treatment group(Tg+Ator group).Atro at 10 mg· kg-1-d-1was administered to the mice in all Ator groups from the 5th week.The mice in the control groups were given saline.All these mice were fed for 13 weeks.Oil red O staining and HE staining of the aortic wall of the mice were used to measure the atherosclerotic le-sion burdens.The protein levels of HSP22,NF-κB, eNOS, ICAM-1 and IL-6 in the aorta and serum were examined by Western blot,immunohistochemistry and ELISA.RESULTS:Aortic Oil red O staining and HE staining showed that the relative area of aorta plaque in Tg group was less than that in KO group(P<0.05).The protein expression of HSP22 in Tg group was significantly higher than that in control group and KO group,and its expression in control group was signifi-cantly higher than that in KO group.The protein expression of eNOS in Tg group and control group was significantly higher than that in KO group.The protein expression of NF-κB and ICAM-1 in control group was significantly decreased as com-pared with KO group,and their expression was significantly higher than that in Tg group.No difference of serum IL-6 level was found among Tg group,KO group and control group.CONCLUSION:HSP22 gene deletion up-regulates the expres-sion of NF-κB and ICAM-1,and down-regulates the expression of eNOS,leading to accelerating AS.HSP22 overexpression decreases the expression of NF-κB and ICAM-1 and increases the expression of eNOS,thus attenuating AS development. HSP22 gene deletion partially limits the role of Ator in the expression of NF-κB,ICAM-1 and eNOS.HSP22 overexpression amplifies the reduced expression of ICAM-1 by the intervention with Ator,and further attenuates AS development.

2.
Chinese Circulation Journal ; (12): 454-458, 2016.
Article in Chinese | WPRIM | ID: wpr-492595

ABSTRACT

Objective: To study the dynamic changes of type Th22 cell immunological response during atherosclerosis process in experimental mice in order to provide a new theoretical basis for atherosclerosis therapy. Methods: 8 weeks C57BL/6J mice were divided into 2 groups: Experiment group,n=24 ApoE-/- mice and Control group, n=24 normal mice. All animals received high fat diet and the following indexes were compared between 2 groups at 0, 4, 8, 12 weeks after treatment: aortic atherosclerotic lesions were deifned by Oil red O staining, dynamic changes of Th22 cells in spleen were measured by lfow cytometry, mRNA expressions of interleukin-22 (IL-22), IL-22R1, AhR and T-bet in aorta were examined by RT-PCR, blood levels of IL-22 was detected by ELISA. Results: Compared with Control group, Experiment group had the increased area of aortic atherosclerosis (the ratio of plaque area/lumen area) and Th22 cell (CD4+ IL-22+/CD4+T cell) amount, elevated mRNA expressions of IL-22, IL-22R1, AHR, T-bet in aorta and higher blood levels of IL-22 at all time points, the differences between each time point (except 0 week) had the statistic meaning,P<0.05. In Experiment group, the differences between 2 adjacent time points, for the area of aortic atherosclerosis and mRNA expressions of AHR, T-bet: 4 weeks vs 0 week, 8 weeks vs 4 weeks, 12 weeks vs 8 weeks all had statistic meaning; for Th22 cell amount: 4 weeks vs 0 week, 8 weeks vs 4 weeks had statistic meaning and 12 weeks vs 8 weeks had no real distinction; for mRNA expressions of IL-22, IL-22R1 and blood levels of IL-22: 4 weeks vs 0 week had statistic meaning and 8 weeks vs 4 weeks, 12 weeks vs 8 weeks had no real distinctions. Conclusion: Hyperactive immunological response of Th22 cells might be involved in atherosclerosis process, the relevant mechanism should be further studied.

3.
Chinese Journal of Microbiology and Immunology ; (12): 995-999, 2012.
Article in Chinese | WPRIM | ID: wpr-429349

ABSTRACT

Objective To investigate the association between IL-22 and the pathogenesis of coronary artery atherosclerosis(AS).Methods The relative expression of IL-22 mRNA in PBMC from 30 AS patients and 8 patients without any signs of coronary artery stenosis was detected by RT-PCR.Serum IL-22 levels of 22 patients without any signs of coronary artery stenosis and 79 AS patients were detected by ELISA.CRL-1730 cells(human umbilical vein endothelial cells) were stimulated with oxidized low density lipoprotein (ox-LDL) at different dosage for 24 h,and the expression of IL-22R1 was detected by flowcytometry.The proliferation ability of CRL-1730 cells treated with IL-22(20 ng/ml) and/or ox-LDL(100 μg/ml)was measured by MTS assay,and the expression of basic fibroblast growth factor(bFGF) was detected by RTPCR and ELISA.Results Decreased IL-22 expression in PBMC and serum was observed as worsen of AS.The expression of IL-22R1 in ox-LDL treated CRL-1730 cells was increased in dose dependent manner.OxLDL decreased proliferation ability,as well as bFGF expression and releasing,of CRL-1730 cells.This effect of ox-LDL was partially rescued by IL-22.Conclusion IL-22 may have anti-atherosclerosis effect.This effect may be mediated by regulating bFGF expression and endothelial cells proliferation ability in the presence of IL-22.

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