目的探讨血管紧张素Ⅱ受体拮抗剂替米沙坦对小鼠3T3-L1脂肪细胞合成白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的影响。方法脂肪细胞诱导至90%成熟,随机分为5组:对照组,脂多糖(LPS)组,LPS+替米沙坦组,其中替米沙坦设0.1μg/ml、1μg/ml和10μg/ml 3个浓度梯度。对照组中加DMSO,LPS+替米沙坦组中加不同浓度替米沙坦,孵育2h后,再向LPS组和LPS+替米沙坦组加入LPS(1μg/ml),与替米沙坦共同孵育细胞1h。酶联免疫吸附法(ELISA)检测各组IL-6和TNF-α的蛋白分泌水平,Q-PCR检测各组IL-6和TNF-αmRNA基因表达。结果脂多糖处理后IL-6分泌较对照组增加约2.7倍,IL-6mRNA表达增加4倍。替米沙坦干预后各组IL-6浓度较脂多糖组均明显下降,10μg/ml组降低67%,IL-6mRNA表达随替米沙坦浓度升高而下降,10μg/ml组下降约63%。此外,与对照组相比,脂多糖处理组TNF-α分泌增加1.3倍,其mRNA表达增加3.5倍,替米沙坦干预后,各组TNF-α蛋白分泌及mRNA表达均较脂多糖组明显降低,大剂量替米沙坦干预后(10μg/ml),TNF-α蛋白分泌下降约85%,mRNA表达下降约23%。结论替米沙坦通过影响脂肪细胞炎性因子的产生发挥抗炎作用,10μg/ml大剂量时作用尤为明显。
Objective To study the effect of telmisartan,an angiotensin Ⅱ receptor antagonist,on production of IL-6 and TNF-α in 3T3-L1 adipose cells of mice.Methods 3T3-L1 adipose cells were randomly divided into control group,lipopolysaccharide(LPS) group,LPS+0.1μg/ml telmisartan group,LPS + 1μg/ml telmisartan group,LPS+10μg/ml telmisartan group.After DMSO was added into LPS group and telmisartan was added into LPS + telmisartan group at different concentrations,the cells were incubated for 2h.Then,1μg/ml LPS was added into LPS group and LPS + telmisartan group,the cells were co-incubated with telmisartan for 1h.The secretion levels of IL-6 and TNF-α were measured by ELISA and the expression of IL-6 and TNF-α mRNA was detected by RT-PCR.Results The secretion level of IL-6 and the expression level of IL-6 mRNA in 3T3-L1 adipose cells were 2.7-fold and 4-fold higher,respectively,in LPS group than in control group after treatment with LPS.The IL-6 level and the IL-6 mRNA expression level were significantly lower in other groups than in LPS group after treatment with telmisartan,which were decreased to 67% and 63%,respectively,after treatment with 10μg/ml telmisartan.The secretion level of TNF-α and the expression level of TNF-α mRNA were 1.3-fold and 3.5-fold higher in LPS group than in control group,and significantly lower in other groups than in LPS group after treatment with telmisartan,which decreased about 85% and 23% after treatment with 10μg/ml telmisartan.Conclusion Telmisartan can exert its anti-inflammation effect by inhibiting the production of inflammatory factors in 3T3-L1 adipose cells,especially when it is used at the concentration of 10μg/ml.