CAJ | 학술논문

目的：探讨吡格列酮对载脂蛋白E( ApoE)-/-小鼠主动脉粥样硬化病变中Toll样受体4/丝裂原活化蛋白激酶(TLR4/MAPKs)信号通路的影响。方法取8只10周龄雄性C3H小鼠作为对照组,用普通饲料喂养；另取24只同周龄雄性ApoE-/-小鼠用高脂饲料喂养,复制动脉粥样硬化模型成功后按随机数表法分成3组：模型组、吡格列酮低剂量(5 mg·kg-1·d-1)组和高剂量(10 mg·kg-1·d-1)组各8只。干预4周后,HE染色观察主动脉粥样硬化病变情况。应用Western Blot技术检测对照组和干预组动脉粥样硬化中丝裂原活化蛋白激酶ERK1/2、JNK1/2及p38MAPK磷酸化水平。结果与对照组比较,各组ApoE-/-小鼠动脉粥样硬化斑块中TLR4表达增强,其中ERK1/2与JNK磷酸化水平明显升高(均为P﹤0.05),但p38MAPK水平变化不明显(均为P＞0.05)；与模型组比较,吡咯列酮低剂量组和高剂量组小鼠动脉粥样硬化斑块中ERK1/2与JNK磷酸化水平均降低( ERK1/2：吡咯列酮低剂量组比模型组：0.5037±0.0438比0.8800±0.0436,吡咯列酮高剂量组比模型组：0.3843±0.0236比0.8800±0.0436；JNK：吡咯列酮低剂量组比模型组：0.5037±0.0437比0.7900±0.0308,吡咯列酮高剂量组比模型组：0.3843±0.0237比0.7900±0.0308,均为P﹤0.05)。结论吡格列酮可能通过影响TLR4/MAPKs/ERK1/2与TLR4/MAPKs/JNK信号通路,延缓动脉粥样硬化的发生与发展。
목적：탐토필격렬동대재지단백E( ApoE)-/-소서주동맥죽양경화병변중Toll양수체4/사렬원활화단백격매(TLR4/MAPKs)신호통로적영향。방법취8지10주령웅성C3H소서작위대조조,용보통사료위양；령취24지동주령웅성ApoE-/-소서용고지사료위양,복제동맥죽양경화모형성공후안수궤수표법분성3조：모형조、필격렬동저제량(5 mg·kg-1·d-1)조화고제량(10 mg·kg-1·d-1)조각8지。간예4주후,HE염색관찰주동맥죽양경화병변정황。응용Western Blot기술검측대조조화간예조동맥죽양경화중사렬원활화단백격매ERK1/2、JNK1/2급p38MAPK린산화수평。결과여대조조비교,각조ApoE-/-소서동맥죽양경화반괴중TLR4표체증강,기중ERK1/2여JNK린산화수평명현승고(균위P﹤0.05),단p38MAPK수평변화불명현(균위P＞0.05)；여모형조비교,필각렬동저제량조화고제량조소서동맥죽양경화반괴중ERK1/2여JNK린산화수평균강저( ERK1/2：필각렬동저제량조비모형조：0.5037±0.0438비0.8800±0.0436,필각렬동고제량조비모형조：0.3843±0.0236비0.8800±0.0436；JNK：필각렬동저제량조비모형조：0.5037±0.0437비0.7900±0.0308,필각렬동고제량조비모형조：0.3843±0.0237비0.7900±0.0308,균위P﹤0.05)。결론필격렬동가능통과영향TLR4/MAPKs/ERK1/2여TLR4/MAPKs/JNK신호통로,연완동맥죽양경화적발생여발전。
Objective To study the effects of piogitazone on Toll-like receptor 4/MAPKs pathway in atherosclerosis of apolipoprotein E knockout (ApoE-/ -) mouse. Methods The 8 male mice of C3H, 10 weeks aged, were fed with common food for 4 weeks as control group. In addition, The same age male mice of ApoE-/ - fed with high fatty food for setting up atherosclerosis animal models were selected as experimental group ( n=24 ) , and the experimental mice were randomly divided into three groups: model group only receiving high fatty food for 6 weeks, low-dose treated group receiving piogitazone administered via gastric tube at 5 mg·kg-1·d-1 for consecutive 6 weeks and high-dose treated group receiving piogitazone administered via gastric tube at 10 mg·kg-1·d-1 for consecutive 6 weeks. The expression of pERK1/2, JNK and p38MAPK, and levels of their phosphorylation were measured by Western blotting in control group and experimental group. Results The expression of TLR4 was significantly increased in all ApoE-/ - mice than in control group (P ﹤0. 01). Compared with the control group, the activities of p-ERK1/2 and p-JNK were significantly increased in each experimental group (P ﹤ 0. 05), but the expression level of p38MAPK was similar among the groups (P > 0. 05). Compared with model group, the expressions of p-ERK1/2 and p- JNK were significantly decreased (P ﹤ 0. 05), moreover, these changes were more significant in high-dose treated group (for ERK1/2: 0. 5037 ± 0. 0438 in low-dose treated group, 0. 3843 ± 0. 0236 in high-dose treated group, and 0. 8800 ±0. 0436 in control group; for JNK: 0. 5037 ±0. 0437 in low-dose treated group, 0. 3843 ± 0. 0237 in high-dose treated group and 0. 7900 ± 0. 0308 in control group, all P ﹤ 0. 05) .