高剂量绿原酸对脂多糖诱导肝脏炎症因子mRNA表达的影响

EFFECT OF CHLOROGENIC ACID AT HIGH DOSE ON EXPRESSION OF HEPATIC INFLAMMATORY CYTOKINES mRNA INDUCED BY LIPOPOLYSACCHARIDES

目的研究不同剂量绿原酸(5-CQA)在非炎症及脂多糖(LPS)诱导急性炎症条件下,对肝组织炎症反应的影响。方法雄性C57BL/6小鼠48只,随机分为空白对照(NC)、LPS诱导模型(LM)、绿原酸+LPS干预[5-CQA(mg/kg·d)低(LA50)、中(LA100)、高剂量(LA200)]、5-CQA(mg/kg·d)低、中、高剂量(A50,A100,A200)共8组,NC和LM组灌胃蒸馏水,其余组灌胃不同剂量绿原酸。饲喂10d后处死,取血清检测谷草转氨酶(AST)和谷丙转氨酶(ALT)活性;采集肝脏制备HE染色切片观察病理情况,实时荧光定量PCR方法测定肝脏组织肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、一氧化氮合成酶(iNOS)、环氧合酶(COX-2)mRNA的表达。结果 LA200组显著提高LPS诱导的急性炎症小鼠血清AST和ALT活性。同时,可显著促进急性炎症小鼠肝脏TNF-α、IL-6、IL-1β、iNOS、COX-2 mRNA表达。切片结果显示LA200组肝组织发生了巨噬细胞聚集,细胞核退化和细胞水肿现象。结论 LPS诱导急性炎症下,前期5-CQA的摄入并不能降低血清ASL、ALT活性、减少炎症因子表达,5-CQA 200mg/kg·d甚至会促进炎症因子表达,加强LPS诱导的肝脏急性炎症反应。

Objective To investigate the effects of different doses of 5-caffeoylquinic acid （5-CQA） on hepatic inflammation in the conditions of non-inflammation and acute inflammation induced by lipopolysaccharide. Methods Forty-eight male C57BL/6J mice were randomly divided into 8 groups： control（NC）, LPS model（LM）, 5-CQA ＋ LPS[low（LA50）, medium（LA100） and high（LA200） doses of 5-CQA], 5-CQA（low, medium and high doses of 5-CQA, A50, A100, A200）. NC and LM groups were given distilled water, while other groups were given different doses of 5-CQA. All mice were sacrificed after 10d feeding and serum AST and ALT were detected. Expressions of TNF-α, IL-6, IL-1β, iNOS, COX-2 mRNA were assessed by RT-PCR. Histological changes of the liver in the LPS-treated mice were examined by hematoxylin and eosin staining. Results LA200 could not only improve significantly the activity of serum AST and ALT, but also enhance the expressions of TNF-α, IL-6, IL-1β, iNOS and COX-2 mRNA in mice with acute inflammation. The histological study revealed that there were macrophage accumulation, nuclear degradation and cellular edema in hepatic tissue. Conclusion When LPS-induced inflammation occurred, 5-CQA could not decrease the activities of ASL, ALT in serum or the expression of inflammatory factors. 5-CQA at the dose of 200 mg/kg· d even may promote the expression of inflammatory factors and enhance inflammation reaction in hepatic tissue.