血小板活化因子在幼年大鼠肠道免疫屏障功能损伤中的作用

Role of platelet activating factor in the injury of intestinal immuno-barrier function in young rats

摘要:

目的：胃肠功能障碍与严重感染引起的肠屏障功能破坏密切相关。血小板活化因子(plateletactivatingfactor,PAF)可引起肠损伤。该文应用PAF受体拮抗剂研究PAF对幼年大鼠肠黏膜免疫屏障功能损伤作用。方法：18日龄Wistar大鼠,随机分为LPS组和PAF受体拮抗剂组(预防组和治疗组)及对照组。LPS组和对照组分别腹腔注射内毒素5mg/kg及生理盐水1mL/kg,每一时相点8只,分别于注射后1.5,3,6,24,48,72h取回肠。预防组和治疗组分别于每一时相点注射LPS前、后30min腹腔注射PAF受体拮抗剂BN520215mg/kg。应用双抗体PEG放免法测定肠黏膜中分泌型IgA(secretoryIgA,sIgA)含量。苏木精伊红染色作形态学检查,并称湿(W)干(D)重,按照WD/W,以其%计算湿干比。结果：1.5,3,6,24hLPS组可见回肠绒毛水肿,固有层血管充血,间质淋巴管扩张,肠腔炎性渗出,拮抗剂组仅见绒毛水肿。实验组各时相点湿干比均较对照组升高,拮抗剂组较LPS组略低。LPS组1.5,3,6,24,48hsIgA均较对照组明显降低P<0.01。拮抗剂组各时相点sIgA均较LPS组高,预防组较治疗组sIgA略低。结论：PAF在肠黏膜的免疫屏障功能损伤中起一定作用,预防和治疗性应用PAF受体拮抗剂BN52021可减轻肠损伤。

Abstract:

OBJECTIVE: Gastrointestinal dysfunction is closely correlated with the destruction of intestinal barrier function induced by serious infection. Platelet activating factor (PAF) may induce intestinal injuries. This study aimed to investigate the effect of PAF on the injury of intestinal mucosal immuno-barrier function in young rats. METHODS: Eighteen-day-old Wistar rats were randomized to lipopolysaccharide(LPS) (5 mg/kg), LPS plus PAF receptor antagonist and normal saline injection(Control). PAF receptor antagonist BN52021 5 mg/kg was administered before or 30 minutes after LPS injection (pretreatment or treatment). The ileum specimens (n=8) were harvested at 1.5, 3, 6, 24, 48 and 72 hrs after LPS injection. Double antibody-PEG radioimmunoassay was used to determine the secretory IgA(sIgA) content in intestinal mucosa. Hematoxylin and erosin staining was used for histological evaluation. The ratio of wet and dry weight (W/D) of ileum tissues was calculated. RESULTS: Intestinal villi edema, capillary congestion, extension of the subepithelial lympho channel, and polymorphonuclear infiltration in enteric cavity were noted in the LPS group at 1.5, 3, 6 and 24 hrs after LPS injection. In the PAF receptor antagonist group only villi edema was found. The W/D ratio in the LPS group was significantly higher than that in the Control group at all time points, but it was slightly reduced by the PAF receptor antagonist pretreatment or treatment. The sIgA content was obviously decreased after 1.5, 3, 6, 24 and 48 hrs of LPS challenge compared with that in the Control group (P<0.01). It reached to a nadir at 6 hrs (0.15±0.04 μg/mL). The level of sIgA in the PAF receptor antagonist group was higher than that in the LPS group at each time point. There was no statistical difference in the sIgA level between the PAF receptor pretreatment and treatment groups. CONCLUSIONS: PAF plays roles in the injury of intestinal immuno-barrier function. Preventive and remedial use of PAF receptor antagonist BN52021 may relieve intestinal injury.