摘要
目的观察在高脂环境下五指山小型猪、西藏小型猪血脂和炎症细胞的变化,分析冠心病相关血脂和炎症易感基因的表达。方法取雄性五指山小型猪、西藏小型猪各5只,高脂饲喂连续6个月,每月检测血脂和血常规,并检测饲喂前和饲喂6个月时外周白细胞中LDLR、LPL、PCSK9、ApoAV、5-LO、FLAP、MMP-9、ICAM-1、VCAM-1基因和蛋白的表达,及血清中CRP、TNF-α水平;并在饲喂6个月时取腹主动脉组织进行HE染色病理学检查。结果高脂饲喂后,两种小型猪TC、HDL-C、LDL-C水平均显著升高(P<0.01),西藏小型猪WBC、NEUT%、MONO%和五指山小型猪MONO%亦呈升高趋势(P>0.05);五指山小型猪TC、LDL-C水平高于西藏小型猪,而西藏小型猪的WBC、NEUT%和MONO%显著高于五指山小型猪(P<0.05,P<0.01),且西藏小型猪血清CRP和TNF-α水平显著升高(P<0.05),而五指山小型猪未见显著差异(P>0.05)。高脂饲喂6个月后,两种小型猪均出现明显的AS斑块,五指山小型猪LDLR、ApoAV mRNA和蛋白表达均显著降低(P<0.05,P<0.01),PCSK9、LPL mRNA表达显著升高(P<0.05,P<0.01);西藏小型猪LPL mRNA和蛋白表达均显著升高(P<0.01);五指山小型猪5-LO、FLAP、ICAM-1、VCAM-1 mRNA表达和5-LO蛋白表达均显著升高(P<0.05,P<0.01),西藏小型猪FLAP、MMP-9、ICAM-1、VCAM-1 mRNA和蛋白表达均显著升高(P<0.05,P<0.01),且西藏小型猪MMP-9、ICAM-1、VCAM-1 mRNA和蛋白表达均高于五指山小型猪,而5-LO mRNA和蛋白表达则五指山小型猪高于西藏小型猪。结论高脂环境下五指山小型猪、西藏小型猪均出现不同程度的血脂异常和炎症反应,两种小型猪的冠心病相关血脂和炎症易感基因存在明显异质性,其中,高脂诱导下五指山小型猪外周血白细胞对LDLR、PCSK9、5-LO表达较敏感,而西藏小型猪外周血白细胞中对LPL、ICAM-1、VCAM-1和MMP-9表达较敏感。
Objective To observe the changes in blood lipid and inflammatory cells in Wuzhishan (WZS) minipigs and Tibetan minipigs exposed to a high-fat diet environment, and to analyze the expressions of coronary artery disease-related blood lipid and inflammatory susceptibility genes. Methods Five male WZS minipigs and five Tibetan minipigs were selected for feeding with a high-fat diet for six consecutive months. Blood lipids and blood routine examination were performed monthly, and venous blood was taken before and 6 months after high-fat feeding to determine the gene and protein expression levels of LDLR, LPL, PCSK9, ApoAV, 5-LO, FLAP, MMP-9, ICAM-1 and VCAM-1 in peripheral leukocytes, as well as the levels of CRP and TNF-α. Thoracic aorta samples were taken for pathological examination after high-fat feeding for 6 consecutive months. Results After high-fat diet feeding, the levels of TC, HDL-C, and LDL-C in the two minipigs were significantly increased (P<0. 01), and WBC, NEUT% and MONO% in the Tibetan minipigs as well as MONO% in the WZS minipigs tended to be increased (P>0. 05). TC and LDL-C levels in the WZS minipigs were higher than those in the Tibetan minipigs, whereas WBC, NEUT% and MONO% in the Tibetan minipigs were much higher than those in the WZS minipigs (P<0. 05, P<0. 01). After high-fat feeding for 6 months, there were obvious atherosclerotic (AS) plaques in the two minipigs, but the degree of AS lesions in the Tibetan minipigs was more serious. The mRNA and protein expressions of LDLR and ApoAV in the WZS minipigs were markedly decreased (P<0. 05, P<0. 01), whereas the mRNA expressions of PCSK9 and LPL were markedly increased (P<0. 05, P<0. 01). The mRNA and protein expressions of LPL in the Tibetan minipigs were obviously increased (P<0. 01). Moreover, the mRNA expressions of 5-LO, FLAP, ICAM-1 and VCAM-1, and protein expression of 5-LO in the WZS minipigs were significantly increased (P<0. 05, P< 0. 01). mRNA and protein expressions of FLAP, MMP-9, ICAM-1, and VCAM-1 in the Tibetan minipigs were markedly increased (P<0. 05, P<0. 01). Moreover, mRNA and protein expressions of MMP-9, ICAM-1, and VCAM-1 in Tibetan minipigs were higher than those in the WZS minipigs, whereas mRNA and protein expressions of 5-LO were lower. Conclusions WZS and Tibetan minipigs have various degrees of dyslipidemia and inflammation under a high-fat diet environment. Significant heterogeneity exists in CAD-related blood lipids and inflammatory susceptibility genes. The expressions of LDLR, PCSK9, and 5-LO in the peripheral leukocytes are more affected in WZS minipigs, while LPL, ICAM-1, VCAM-1, and MMP-9 in the peripheral leukocytes are more affected in Tibetan minipigs.
作者
郁晨
刘志华
潘永明
徐孝平
徐剑钦
杨钦钦
蔡兆伟
陈民利
YU Chen;LIU Zhihua;PAN Yongming;XU Xiaoping;XU Jianqin;YANG Qinqin;CAI Zhaowei;CHEN Minli.(Laboratory Animal Research Center/ Comparative Medical Research Institute,Zhejiang Chinese Medical University, Hangzhou 310053, China)
出处
《中国比较医学杂志》
CAS
北大核心
2019年第5期1-10,共10页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金项目(31572346)
关键词
高脂环境
五指山小型猪
西藏小型猪
血脂
炎症
易感基因
high-fat diet environment
Wuzhishan minipig
Tibetan minipig
blood lipid
inflammation
susceptibility genes
