穿心莲内酯调控JAK2/STAT3信号通路对佐剂诱导的小鼠脚掌炎性肿胀的抗炎作用

Anti-inflammatory effect of andrographolide on adjuvant-induced inflammatory paw swelling in mice via the JAK2/STAT3 signaling pathway

目的:探讨穿心莲内酯对完全弗式佐剂(CFA)诱导的小鼠脚掌炎性肿胀的抗炎作用及其机制。方法:将60只昆明小鼠随机分为空白对照组、模型组、地塞米松(Dex)阳性对照组(2 mg/kg)以及穿心莲内酯高、中、低剂量组(300 mg/kg、150 mg/kg、75 mg/kg)。灌胃给药10 d后,除空白对照组外,其他各组均于小鼠右后足踝部注射CFA 20μL,复制小鼠足肿胀急性炎症模型。观察小鼠脚掌肿胀变化,计算脾脏指数,酶联免疫吸附试验(ELISA)法测定小鼠血清肿瘤坏死因子(TNF)-α水平;Western blot法检测磷酸化(p-)Janus激酶(JAK2)、p-信号转导子和转录激活子3(STAT3)蛋白表达。结果:与空白对照组比较,模型组小鼠脚掌明显肿胀,脾脏指数、TNF-α水平及p-JAK2、p-STAT3蛋白表达量明显升高(P<0.05);与模型组相比,穿心莲内酯可显著降低小鼠脚掌肿胀厚度以及脾脏指数,降低TNF-α的含量,抑制p-JAK2、p-STAT3的蛋白表达(P<0.05)。结论:穿心莲内酯可能通过阻断JAK2/STAT3信号通路,抑制CFA诱导小鼠脚掌炎性肿胀。

Objective:To investigate the anti-inflammatory effect and its mechanism of andrographolide on the complete Freund’s adjuvant(CFA)-induced inflammatory paw swelling in mice.Methods:Sixty Kunming mice were randomly divided into blank control group,model group,dexamethasone(Dex)positive control group(2 mg/kg)and andrographolide high,medium and low dose groups(300 mg/kg,150 mg/kg,75 mg/kg).After intragastric administration for 10 days,CFA 20μL was injected into the right hind ankle of the mice except for the blank control group in order to establish the model of mouse paw swelling and acute inflammation.The swelling of mouse paw was observed,the spleen index was calculated,and the serum tumor necrosis factor(TNF)-αlevel in the mice was measured by enzyme-linked immunosorbent assay(ELISA)method.Western blot method was used to detect the protein expression of phosphorylation(p-)Janus kinase 2(JAK2),p-signal transducer and activator of transcription 3(STAT3).Results:Compared with the blank control group,the paw swelling in the model group,and the spleen index,TNF-α level,and p-JAK2,p-STAT3 protein expression were all significantly increased in the model group(P<0.05).Comparison to the model group,andrographolide can significantly reduce swelling thickness,spleen index,the TNF-α content,and inhibit the protein expression of p-JAK2 and p-STAT3 in mice in andrographolide group(P<0.05).Conclusion:Andrographolide may inhibit CFA-induced inflammatory paw swelling in the feet of mice by blocking the JAK2/STAT3 signaling pathway.