探讨普萘洛尔对大鼠肝大部分切除术后肠道细菌移位的影响。

45只大鼠按随机数字表法随机分为假手术组（SO组）、肝大部分切除组（PH组）和肝大部分切除+普萘洛尔组（PHP组），每组15只。SO组大鼠术后给予生理盐水2 ml灌胃；PH组和PHP组大鼠切除肝左叶和肝中叶，切除的肝脏体积约为大鼠肝脏体积的70%，PH组术后给予生理盐水2 ml灌胃，PHP组术后给予5 mg/ml的普萘洛尔溶液2 ml灌胃，12 h后各组重复给药1次。术后24 h再次开腹，测定门静脉压力，抽取门静脉血检测血浆内毒素、D-乳酸变化，摘取肠系膜淋巴结行细菌培养及鉴定，计算细菌移位率，切取小肠壁用光镜和电镜观察小肠黏膜损伤情况，并进行小肠黏膜损伤评分。采用单因素方差分析和LSD-t检验比较3组大鼠门静脉压力、血浆内毒素及D-乳酸变化；采用Fisher确切概率法比较3组细菌移位率；采用Kruskal Wallis test和Mann-Whitney非参数检验比较小肠黏膜损伤评分变化。

PH组大鼠门静脉压力（13.8±2.4）cm H₂O（1 cmH₂O=0.098 kPa），显著高于SO组的（8.2±2.0）cm H₂O和PHP组的（10.8±2.4）cm H₂O（t=6.84、3.38，均为P<0.01)。PH组大鼠血浆内毒素（13.7±4.1）pg/ml，高于SO组的（2.0±0.5）pg/ml和PHP组（6.8±2.0）pg/ml（t=9.44、5.26，均为P<0.01）。SO组、PH组、PHP组大鼠分别有1、8、3只发生肠道细菌移位，细菌移位率分别为7%、53%、20%，PH组大鼠细菌移位率与SO组和PHP组比较差异均有统计学意义（均为P<0.05），细菌培养主要为大肠埃希菌。PH组的血浆D-乳酸水平（26±5）mg/ml，高于SO组的（6±3）mg/ml和PHP组的（15±4）mg/ml（t=13.08、6.49，均为P<0.01）。PH组大鼠小肠黏膜损伤评分的中位数（5分）较SO组（1分）和PHP组（3分）高（U=47.33、38.64，均为P<0.01）。SO组大鼠小肠黏膜完整，连续的黏液层覆盖在上皮细胞上；PH组表现为不同程度的绒毛破坏，绒毛缩短、局灶性损害，细胞线粒体肿胀或消失、线粒体脊退化，细胞间隙增宽等变化；PHP组大鼠上述几项指标介乎于SO组和PH组之间。

普萘洛尔能降低大鼠肝大部分切除术导致的门静脉压力升高，增强肠黏膜屏障功能，有效减少术后肠道细菌移位的发生率，因而术后普萘洛尔灌胃可用于预防大鼠肝大部分切除术后感染。

To investigate the effects of propranolol on bacterial translocation in rats after major liver resection.

Forty five rats were randomly divided into three groups, sham operation group (SO group, n=15), 70% partial hepatectomy group (PH group, n=15) and 70% partial hepatectomy plus propranolol group(PHP group, n=15). The rats in SO group received gastric perfusion with 2 ml normal saline. The rats in the PH and PHP groups had 70% of their liver left and middle lobes resected. The rats in the PH group were given gastric perfusion of 2 ml normal saline and those in the PHP group were given gastric perfusion of 2 ml propranolol solution (5 mg/ml) after operation and the treatment was repeated 12 hours later. All rats underwent laparotomy 24 hours later after operation. Portal pressure, blood endotoxin and D-lactic acid were measured. Mesenteric lymph nodes were harvested for standard bacteriologic culture and characterization. Intestinal wall was resected for observing intestinal mucosal injury by light microscope and electron microscope. Bacterial translocation rate was calculated. The intestinal mucosal injury was graded. One-way analysis of variance and LSD-t test were used to compare the change of the portal pressure, blood endotoxin and D-lactic acid among 3 groups. Fisher definite probability method was used to compare the bacterial translocation rate. Kruskal-Wallis and Mann-Whitney test were used to compare the intestinal mucosal injury.

The portal pressure of rats in the PH group rats (13.8±2.4)cm H₂O was significantly higher compared with the SO(8.2±2.0)cm H₂O and PHP group(10.8±2.4)cm H₂O (t=6.84, 3.38; all in P<0.01). The blood endotoxin levels decreased significantly in the PHP (6.8±2.0)pg/ml and SO group groups (2.0±0.5)pg/ml compared with PH (13.7±4.1)pg/ml (t=9.44, 5.26; all in P<0.01). There were 1, 8, 3 rats with bacterial translocation in the SO, PH and PHP group with 53%,7%,20% of bacterial translocation rate respectively. There was significant difference in bacteria translocation rate between the PH group and the other groups(all in P<0.05). The bacteria culture showed that Escherichia coli were the main bacteria. D-lactic acid in the PH group rats (26±5)mg/ml was significantly higher compared with the SO(6±3) mg/ml and PHP(15±4)mg/ml group(t=13.08, 6.49; all in P<0.01). The median of intestinal mucosal injury scores was significantly higher in the PH group rats (5), compared with the SO(1) and PH (3)group (U=47.33, 38.64; all in P<0.01) . The intestinal mucosa of rats in the SO group was intact with continuous slime layer over the epithelial cells. On the contrary, the rats in the PH group had destroyed microvilli of different degree, focal damage, swollen or disappeared cellular mitochondria, degeneration of mitochondrial ridges and widened cell gaps. The damage degree of intestine mucosa in the PHP group was between the SO and PH group.

Propranolol can reduce the portal pressure, enhance the intestinal barrier function, diminish the bacterial translocation. Therefore, intragastric gavaging with propranolol can prevent the postoperative infection in rats undergoing major liver resection.