PGE2对创伤弧菌攻击肝病大鼠肝组织的保护作用

The study of pathogenesis and immuno-protection on vibrio vulnificus

目的研究创伤弧菌(Vibriovulnificus,Vv)致病机制,进而探讨前列腺素E(2prostaglandin-E2,PGE2)对Vv感染免疫保护作用,为Vv感染的预防和临床治疗提供实验依据。方法取18只正常大鼠和36只慢性肝病大鼠,随机分成:①正常氧氟沙星治疗组;②正常PGE2免疫干预与氧氟沙星联合保护组;③肝病氧氟沙星等药物治疗组;④肝病PGE2免疫干预与氧氟沙星等药物联合保护组;⑤肝病大鼠阴性对照组;⑥肝病大鼠Vv攻击对照组(n=9)。①与③组腹腔注射Vv菌液0.4m(l约6.0×107cfu/只)1h后,再肌肉注射氧氟沙星、异丙嗪和泼尼松尼药液0.4ml,②与④组肌肉预注射0.2mlPGE2溶液2h后,腹腔注射等量Vv菌液1h后肌肉注射等剂量氧氟沙星等药液,⑤组腹腔注射相同剂量NS,⑥组腹腔注射等量Vv菌液。观察各组24h存活数,比较生存率差异。心脏采血并分离血清,按试剂盒说明书步骤检测血清IL-10、IL-1β和IL-6、并作统计学处理,比较组间差异。取肝标本固定、包埋、制成切片在电镜下观察其超微结构改变。结果无论是正常大鼠还是肝病大鼠,与其氧氟沙星治疗组相比,PGE2免疫干预后,IL-10都显著升高(P<0.01,P<0.01),IL-1β、IL-6、浓度则明显降低(均为:P<0.01)。虽然24h生存率没有明显差异(P>0.05),但肝超微结构得以改善。结论PGE2免疫干预在Vv感染中能够上调IL-10并抑制IL-1β、IL-6的分泌,联合氧氟沙星等药物治疗能更有效减轻肝组织细胞损伤。

Objective To study Pathogenesis on Vibrio vulnificus （Vv）, uheriorly to explore immuno-protection effect of prostaglandin E2 to Vv, provide experimental evidences about prevention and clinical treatment of Vv infection.Methods 18 normal rats and 36 chronic hepatopathy rats divided into：①normal ofloxacin protective group; ②normal PGE2 immuno-intervention group;③hepatopathy ofloxacin protective group; ④hepatopathy PGE2 immuno-intervention combined ofloxacin protective group; ⑤hepatopathy negative group; ⑥ hepatopathy Vv protective group （n=9）. ① and ③ were injected intramuscularly ofloxacin 12 mg/kg, promethazine 1mg/kg, pred- nisolone 0.4mg/kg each rat after 6.0×10^7cfu Vv challenged lh; group② and ④ were injected intramuscularly 150μg/kg PGE2 before Vv challenged 2h, then injected isodose ofloxacin, promethazine, prednisolone after challenged 1h. ⑤injected isodose NS, ⑥ injected isodose Vv 0.4ml. Took blood from heart, separated serum and detecteded the concentration of IL-10,IL-1β,IL-6, according to the manual of kits, the data analyzed by the software SPSS10.0. Observed the number of survived rats in 24h and compared the difference of livability. Slices prepared from the tissue of liver, observed uhrastrueture under electron microscope.Results Both normal and hepatopathy PGE2 immuno-intervention groups, contrasted to their ofloxacin protective groups, IL-10 increased distinctly （P〈0.01, P〈 0.01）, IL-1β, IL-6, were obviously enhanced （P〈0.01,）. The uhrastructure of liver improved. Conclusion In Vv primary septicemia, PGE2 immuno-intervention could effectively up-regulation IL-10 and down-regulation IL-1β,IL-6.Adjust the balance of cytokines net. PGE2 combined ofloxacin, promethazine and prednisolone could more effectively treat Vv infection and alleviate the organs damage.