摘要
目的观察过氧化物酶体增殖物激活受体-γ(peroxisome proliferator activated receptors-γ,PPAR-γ)在高血压血管平滑肌细胞(VSMC)表型转化中的作用。方法应用基因重组技术使PPAR-γ过表达和表达抑制,Western blot方法检测分化型VSMC标志物α-SMA和未分化型VSMC标志物OPN的蛋白表达,应用DNA合成率检测和细胞计数的方法测定细胞增殖率,常规病理切片和HE染色观察血管形态学改变。结果PPAR-γ激动剂罗格列酮可降低SHR大鼠血压,并改善主动脉血管重构。②SHR大鼠主动脉中OPN表达增多而α-SMA表达减少,应用罗格列酮可抑制上述改变。③SHR大鼠来源的VSMC中OPN表达增多而α-SMA表达减少,细胞增殖率升高,PPAR-γ过表达使细胞增殖率降低,并抑制OPN和α-SMA的表达改变。结论PPAR-γ可抑制高血压VSMC向未分化表型的转化,可能是其改善高血压血管重构的重要机制。
Objective To observe the effect of peroxisome proliferators activated receptor gamma （PPAR- γ） on phenotypic transforming of vascular smooth muscle cells （VSMC） in hypertension. Methods Spontaneous hypertension rats （SHR） and WKY rats both aged 4 months were included. SHR rats as well as WKY rats were divided to be fed with normal chow, and chow added with rosiglitazone （ 10 mg · kg^-1· d^-1 ） for 16 weeks. VSMC were isolated from SHR rats and WKY rats and cultured by patch-attaching method, then respectively divided into 3 groups after treated with genetic recombination technology： normal VSMC, PPARγ overexpressed VSMC and PPARγ silenced VSMC. Expressions of OPN and α-SMA, which respectively represent the undifferentiated and differentiated VSMC, were detected by Western blotting. Cell proliferation was determined by detecting DNA synthesis and cell counting. The changes of arteries were evaluated pathologically. Results Rosiglitazone decreased blood pressure and ameliorated vascular remodeling of aorta in SHR rats. Aorta of SHR showed an upregulation of OPN and downregulation of α-SMA, which could be inhibited by rosiglitazone. VSMC from SHR rats showed an upregulation of OPN and downregulation of α-SMA, and increased cell proliferation. These changes were all inhibited by rosiglitazone. In the cells that overexpressed PPARγ, the cell proliferation rate was lower, and the expressions of OPN and α-SMA were depressed, compared with the corresponding control cells. Conclusion PPAR-γ could inhibit the phenotypic transforming of VSMC, and this might be responsible for the amelioration of vascular remodeling in hypertension.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2009年第4期311-314,共4页
Journal of Third Military Medical University
基金
重庆市自然科学基金(2006BB5097)
中国博士后科学基金(20070410780)~~
关键词
过氧化物酶体增殖物激活受体-Γ
血管平滑肌细胞
血管重构
表型转化
peroxisome proliferators activated receptor gamma
vascular smooth muscle cells
vascular remodeling
phenotypic transforming
