目的 观察早期微量低分子肝素(LMWH)区域动脉灌注(LAI)后对高脂血症性急性胰腺炎(HLAP)仓鼠模型微循环及病情的影响.方法 健康成年雄性仓鼠共30只,随机均分为3组:区域动脉输注生理盐水组(LAI + saline组)、区域动脉输注低分子肝素组(LAI + LMWH组)和静脉输注低分子肝素组(IV + LMWH组).每组予以高脂饲料(20％猪油+ 10％胆固醇+ 1％丙基硫氧嘧啶+ 1％胆酸钠+ 68. 9％普通饲料)喂养.4周造模成功后,按照Schimidt法,于造模后 30 min 时 LAI + LMWH 组注入 LMWH 20 IU/kg,IV+ LMWH组经静脉输注等量的LMWH,LAI + saline组采取与LAI + LMWH组相同的输注方式注入等容量生理盐水.所有动物造模前经外周静脉注入吖啶橙靶向白细胞荧光染料(2 ml/kg),注射完毕后以激光共聚焦显微镜荧光成像系统动态观察活体动物胰腺微循环,分别于造模前、造模后4 h及6 h 3个时间点检测胰腺微循环血管平均直径(MVD)、功能性毛细血管密度(FCD)及微循环血流速度(MFV)、白细胞黏附水平.6 h后抽取静脉血测定血三酰甘油及血淀粉酶水平,然后处死动物获取胰腺组织,并观察病理学改变,记录胰腺病理学评分.结果 灌注LMWH4 h后的LAI + LMWH组与 IV + LMWH 组及 LAI + saline 组比较,LAI + LMWH 组的胰腺微循环功能指标MVD、FCD、MFV呈显著上升趋势(P<0.05),白细胞黏附数呈明显下降趋势(P<0.05);灌注 LMWH 6 h 后的 LAI + LMWH 组与 IV + LMWH 组及 LAI + saline组比较,LAI +LMWH组的胰腺微循环功能指标MVD、 FCD、MFV呈缓慢上升趋势(P<0. 05),白细胞黏附数呈缓慢下降趋势(P<0. 05),IV + LMWH组与LAI + saline组相比差异无统计学意义;除灌注生理盐水组外,其余各组的胰腺病理学评分较灌注前均有明显改善,4 h时的LAI + LMWH 组改善最显著,6 h时的LAI + LMWH组次之.结论早期区域动脉灌注微量LMWH能明显改善HLAP仓鼠模型微循环功能障碍和病情,对HLAP有显著的治疗作用.%Objective To explore the effects of early giving trace low molecular weight heparin (LMWH) through regional arterial infusion on the pancreatic microcirculation and the severity of hyperlipidemia acute pancreatitis in hamster model. Methods 30 healthy young male hamster were randomly divided into 3 groups with 10 rats in each group: local arterial infusion saline group (LAI + saline group), regional arterial infusion low molecular weight heparin group (LAI + LMWH group) and intravenous low molecular heparin group (IV + LMWH group). Every group were fed with high-fat feed (20％ lard + 10％ cholesterol + 1％ propyl sulfide + 1％ bile acid +68. 9％ general feed). After 4 weeks of successful modeling, according to Schimidt method, LMWH (20 IU/kg) was injected into abdominal aorta at the time that 30 min later from induction finished in LAI + LMWH group; while the same dose LMWH was given through intravenous infusion in IV + LMWH group and the same volume of saline was injected through LAI in LAI + saline group. All animal models were injeccted with acridine orange target white cell fluorescent dyes (2 ml/kg) by peripheral vein before implantation, dynamic observation of pancreatic microcirculation in living animals with laser confocal microscope fluorescence imaging system after injection, detection the variables including MVD, FCD, MFV and leukocyte adhesion level were inspected in vivo by laser confocal microscope at the time of undisterbed, 4 h and 6 h from induction finished. After 6 h, venous blood was taken to measure serum triglyceride and blood amylase. The animals were sacrificed and the pancreas was harvested. Pathological changes and pathological score of pancreas were observed. Results Compared with IV + LMWH group and LAI + saline group in LAI + LMWH group after perfusion LMWH 4 h, the pancreatic microcirculation function index in LAI + LMWH group was significantly increased with MVD, FCD and MFV (P < 0. 05 ), leukocyte adhesion level was decreased significantly (P <0. 05); Compared with IV + LMWH group and LAI + saline group in LAI + LMWH group after perfusion of LMWH 6 h, the function index of pancreatic microcirculation in LAI + LMWH group was increased slowly with MVD, FCD and MFV(P <0. 05); leukocyte adhesion level (a/mm2) showed a slow downward trend(P<0. 05). There was no statistically significant difference between IV + LMWH group and LAI + saline group. In addition to the normal saline group, the pancreatic pathologic scores of the remaining groups were significantly improved before the perfusion, and the LAI + LMWH group improved most significantly at 4 h, while the LAI + LMWH group in 6 h was second. Conclusion Early regional arterial perfusion of LMWH in micro-dose can significantly a-meliorate the microcirculation dysfunction and the severity of HLAP in hamster model, it may exert therapeutic role on HLAP.
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