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多烯磷脂酰胆碱对脓毒症大鼠肝脏的保护作用

[Protective effect of polyenylphosphatidyl choline on liver in rat with sepsis].

作者信息

Zhao Qing-yu, Wang Hao-yuan, Zhang Wen-xiao, Sun Yue-li, Zheng Yi

机构信息

Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in Southern China, Guangzhou 510060, Guangdong, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2011 Jul;23(7):401-4.

PMID:21787467
Abstract

OBJECTIVE

To investigate the protective effect of polyenylphosphatidyl choline (PPC) on liver in rat with sepsis.

METHODS

A total of 50 healthy male SD rats were randomly divided into four groups according to random number table: normal control group (NS group, n=10), sepsis model group (LPS group, n=15), PPC control group (PPC group, n=10) and PPC protection group (P+L group, n=15). A single dose of lipopolysaccharide (LPS) 6 mg/kg was injected to the peritoneal cavity to reproduce the sepsis model, while in NS group and PPC group, same volume of normal saline was used. PPC 10 ml/kg (232.5 mg/kg) was injected 24 hours and 6 hours before LPS via the tail vein in PPC group and P+L group, while in NS group and LPS group 5% glucose solution in the same volume was given. Behavioral changes and mortality rate of rats were recorded, and all survived rats were sacrificed 24 hours after LPS injection. Venous blood was taken for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) determination. Ratios of liver weight/body weight (L/Wb) and wet weight/dry weight of liver (W/D) were calculated. Histopathology changes in liver tissue were observed with hematoxylin eosin (HE) stain, and intercellular adhesion molecule-1 (ICAM-1) expression with instant two-step immunohistochemistry.

RESULTS

Twenty-four hours after LPS injection (LPS group), the rats became lethargic, with less activity and drinking, while rats in P+L group, showed much better mental status, water intake and activity than LPS group. The mortality rate of P+L group was significantly lower than that of LPS group [6.7% (1/15) vs. 46.7% (7/15),P<0.05]. Compared with LPS group, rats in P+L group had lower levels of plasma ALT and AST, L/Wb, W/D , and liver ICAM-1 positive expression ratio [ALT (U/L): 157.71 ± 32.63 vs. 225.63 ± 43.47; AST (U/L): 53.21 ± 13.85 vs. 85.25 ± 18.91; L/Wb: (4.09 ± 0.28)% vs. (4.50 ± 0.25)%; W/D : 3.52 ± 0.27 vs. 3.84 ± 0.18; ICAM-1 positive expression ratio: 35.7% (5/14) vs. 87.5 (7/8),P<0.05 or P <0.01]. All parameters were normal in NS group and PPC group, and no statistical significance was observed between them (all P >0.05). LPS-injection led to severe inflammatory reaction in hepatic tissue , including obvious edema of hepatic parenchymal cells, exudation and aggregation of inflammatory cells, while in P+L group, these morphological changes were milder than that in LPS group but more obvious than that of NS group.

CONCLUSION

Pre-treatment of rats with PPC alleviates progressive inflammatory disturbances of hepatic tissue caused by endotoxin injection, and it attenuates liver edema and ICAM-1 expression, protects liver function and decreases mortality rate in rats with sepsis.

摘要

目的

探讨多烯磷脂酰胆碱(PPC)对脓毒症大鼠肝脏的保护作用。

方法

将50只健康雄性SD大鼠按随机数字表法随机分为四组:正常对照组(NS组,n = 10)、脓毒症模型组(LPS组,n = 15)、PPC对照组(PPC组,n = 10)和PPC保护组(P + L组,n = 15)。向腹腔注射单剂量6 mg/kg脂多糖(LPS)以建立脓毒症模型,而NS组和PPC组注射相同体积的生理盐水。PPC组和P + L组在LPS注射前24小时和6小时经尾静脉注射10 ml/kg(232.5 mg/kg)PPC,而NS组和LPS组给予相同体积的5%葡萄糖溶液。记录大鼠的行为变化和死亡率,所有存活大鼠在LPS注射后24小时处死。采集静脉血测定丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)。计算肝脏重量/体重比(L/Wb)和肝脏湿重/干重比(W/D)。用苏木精-伊红(HE)染色观察肝组织的组织病理学变化,用即时两步免疫组织化学法观察细胞间黏附分子-1(ICAM-1)的表达。

结果

LPS注射后24小时(LPS组),大鼠变得嗜睡,活动和饮水减少,而P + L组大鼠的精神状态、摄水量和活动情况均明显优于LPS组。P + L组的死亡率显著低于LPS组[6.7%(1/15)对46.7%(7/15),P<0.05]。与LPS组相比,P + L组大鼠的血浆ALT、AST水平、L/Wb、W/D以及肝脏ICAM-1阳性表达率较低[ALT(U/L):157.71±32.63对225.63±43.47;AST(U/L):53.21±13.85对85.25±18.91;L/Wb:(4.09±0.28)%对(4.50±0.25)%;W/D:3.52±0.27对3.84±0.18;ICAM-1阳性表达率:35.7%(5/14)对87.5%(7/8),P<0.05或P<0.01]。NS组和PPC组所有参数均正常,两组间无统计学意义(所有P>0.05)。LPS注射导致肝组织严重炎症反应,包括肝实质细胞明显水肿、炎性细胞渗出和聚集,而P + L组这些形态学变化比LPS组轻,但比NS组明显。

结论

PPC预处理大鼠可减轻内毒素注射所致的肝组织进行性炎症紊乱,减轻肝脏水肿和ICAM-1表达,保护肝功能并降低脓毒症大鼠的死亡率。

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