海带多糖对脂多糖致慢性炎症大鼠血管内皮的保护作用

摘要

目的 观察海带多糖 L01对脂多糖(lipopolysaccha-ride,LPS)致慢性炎症大鼠主动脉内皮型一氧化氮合酶(en-dothelial nitric oxide synthase,eNOS)及诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响.方法 尾静脉注射小剂量LPS(0. 4 mg·kg-1 ),每周1 次,持续4周,制备慢性炎症大鼠模型.造模大鼠随机均分为5 组,首次注射LPS 后次日,地塞米松(dexamethasone,DXM)组腹腔注射DXM(10 mg·kg-1 ),L01 高、中、低剂量组分别腹腔注射L01(50、30、10 mg·kg-1 ),LPS 组腹腔注射等体积无菌生理盐水,每天给药1 次.另设对照组,仅注射无菌生理盐水,共计4 周.于末次给药后,采用白细胞(white blood cell,WBC)计数法计数全血WBC 数量;ELISA 法测定大鼠血清中超敏C 反应蛋白(hypersensitive C-reactive protein,hs-CRP)含量;RT-PCR 测定eNOS、iNOS、环氧合酶-2(cyclooxygenase-2,COX-2)mRNA 的表达.结果 L01 给药4 周后可明显降低慢性炎症大鼠全血白细胞数和血清hs-CRP 水平.上调eNOS 表达,下调iNOS 和COX-2 表达.结论 海带多糖L01可能通过调整LPS 刺激下的血管内皮源性舒张因子的表达与释放,改善主动脉内皮依赖型舒张功能,从而对血管内皮的损伤起到一定的保护作用.%Aim To observe the effect of laminarin L01 on the expression of eNOS and iNOS in aorta of rats with chronic inflammation induced by LPS. Methods Chronic inflammatory rat models were prepared by tail vein injection low dose LPS(0.4 mg·kg-1) once a week for four weeks. The rats were randomly divided into five groups. After the first injection of LPS, the DXM group was intraperitoneally injected with dexam-ethasone (10 mg·kg-1). L01 high,medium and low dose groups were intraperitoneally injected with L01 (50,30,10 mg·kg-1). The LPS group was injected intraperitoneally with equal volume of normal saline once a day. Another control group, only injection of normal saline, a total of four weeks. After the last administration,the number of whole white blood cells (WBC) was counted. ELISA was used to measure the hs-CRP in serum. The expressions of eNOS,iNOS and COX-2 mRNA were detected by RT-PCR. Results After four weeks of administration of L01, the number of WBC and the level of serum hs-CRP in chronic in-flammatory rats were significantly decreased. The ex-pression of eNOS was up-regulated, and iNOS and COX-2 expressions were down-regulated. Conclusions Laminarin L01 may regulate the expression and re-lease of endothelium-derived relaxing factor stimulated by LPS,and improve the endothelium-dependent dias-tolic function of aorta, thus protecting the damage of vascular endothelium.