目的 采用實(shí)時(shí)熒光定量PCR（qRT-PCR）法探索全反式維甲酸（ATRA）對兔頸動(dòng)脈粥樣硬化斑塊組織炎癥因子表達(dá)的影響。方法 選取24只純種雄性新西蘭白兔隨機(jī)分為對照組、模型組、ATRA組。對照組給予基礎(chǔ)飼料、其余兩組給予高脂飼料，共飼養(yǎng)12周。飼養(yǎng)4周后，ATRA組ig 5 mg/kg的ATRA，模型組和對照組ig等量溶劑，每天1次，至12周末處死各組動(dòng)物。取頸動(dòng)脈粥樣硬化斑塊組織，進(jìn)行HE染色，顯微鏡下觀察管壁結(jié)構(gòu)；提取組織RNA，qRT-PCR法測定組織中轉(zhuǎn)化生長因子-β1（TGF-β1）、白細(xì)胞介素-10（IL-10）、基質(zhì)金屬蛋白酶-2（MMP-2）和基質(zhì)金屬蛋白酶-9（MMP-9） mRNA的相對表達(dá)量。結(jié)果 模型組可見典型的AS斑塊，可見薄層的纖維帽及大的脂質(zhì)核心，以及大量炎癥細(xì)胞浸潤，內(nèi)彈力纖維膜斷裂；ATRA組內(nèi)皮細(xì)胞形態(tài)基本完整，可見少量炎性細(xì)胞浸潤。與對照組比較，模型組中TGF-β1和IL-10 mRNA的相對表達(dá)量明顯降低（P<0.05），而MMP-2和MMP-9 mRNA的相對表達(dá)量明顯升高（P<0.05）；與模型組比較，ATRA組的TGF-β1和IL-10 mRNA的相對表達(dá)量明顯升高（P<0.05），MMP-2和MMP-9 mRNA的相對表達(dá)量明顯降低（P<0.05）。結(jié)論 ATRA可通過調(diào)節(jié)炎癥因子的表達(dá)抗動(dòng)脈粥樣硬化。

Objective To investigate the effects of all-trans retinoic acid (ATRA) on the inflammatory response in carotid atherosclerotic plaques of rabbit model by using fluorescent quantitative PCR. Methods Twenty-four white purebred male New Zealand rabbits were randomly divided into control group, model group, and ATRA group. The rabbits in the control group were treated with basal feed, while the other two groups were fed with high fat diet. Four weeks later, ATRA group received ATRA ravage at a 5 mg dose once a day and model group received saline ravage at the same dose once a day. After 12 weeks, all rabbits were sacrificed and the carotid atherosclerotic plaques of rabbit were extracted. HE staining was performed and the wall structure was observed under microscope. With the mRNA of GAPDH as internal reference, the relative mRNA expression of TGF-β1, IL-10, MMP-2, and MMP-9 were detected by qRT-PCR. Results The typical AS plaque, thin fibrous cap and large lipid core, infiltration of inflammatory cells and breakage of elastic fibrous membrane were observed in the model group. The endothelial cells in the ATRA group were basically intact with a small amount of inflammatory cells infiltration. Compared with control group, the relative mRNA expression of TGF-β1 and IL-10 were decreased obviously in model group (P < 0.05), while MMP-2 and MMP-9 mRNA were increased significantly (P < 0.05).Compared with model group, the relative mRNA expression of TGF-β1 and IL-10 were increased significantly in ATRA group (P < 0.05), while MMP-2 and MMP-9 mRNA decreased obviously (P < 0.05). Conclusion ATRA can exert anti-atherosclerosis effect by regulating the expression of inflammatory factors.

廣東藥學(xué)院科技處-附屬第一醫(yī)院聯(lián)合自然科學(xué)培育基金項(xiàng)目（GYFYLH201322）；廣州市越秀區(qū)科技計(jì)劃項(xiàng)目（2017-WS-010）