LPS PRETREATMENT PROTECTS FROM HEPATIC ISCHEMIA/REPERFUSION
LPS PRETREATMENT PROTECTS FROM HEPATIC ISCHEMIA/REPERFUSION
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DOI：
10.1006/jsre.1994.1152
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发表时间：
1994-09-01
影响因子：
2.2
通讯作者：
CAMPBELL, DA
中科院分区：
文献类型：
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作者：
COLLETTI, LM;REMICK, DG;CAMPBELL, DA
在啮齿动物体内给予非致死剂量的脂多糖（LPS）可导致对随后致死剂量的内毒素或LPS的保护。我们以前已经证明，肝缺血/再灌注（I/R）的结果在TNF-依赖性肺和肝损伤，我们假设，预处理与亚致死浓度的LPS之前，肝IIR可以保护这种损伤。为了验证这一假设，研究了五组大鼠。LPS-I/R在I/R前24小时静脉内接受25 μ g LPS，VEH-I/R在I/R前24小时静脉内接受等体积的载体，LPS-LPS在假剖腹术前24小时静脉内接受25 μ g LPS，此时静脉内给予另外的25 μ g LPS，在假剖腹手术前24小时，VEH-LPS接受等体积的载体，在假剖腹手术前立即静脉注射25 μ g LPS，而假手术由假手术对照动物组成。血浆肿瘤坏死因子-cu（TNF）水平峰值出现在再灌注30分钟至150分钟之间：LPS-I/ R = 778 +/- 150 pg/ml（n = 5），VEH-I/R = 145 +/- 46 pg/ml（n = 5），LPS-LPS = 970 +/- 716 pg/ml（n = 4），VEH-LPS = 15，949 +/-10，937（n = 5），和假手术= 3 +/-1（n = 5）。如先前由其他研究者证实的，用LPS预处理减少了响应于第二剂量LPS的TNF释放;然而，在用LPS预处理的那些动物中，在肝I/R后TNF释放增加（LPS-I/R vs VEH-I/R，P = 0.014）。通过支气管肺泡灌洗液（BAL）中的总蛋白和细胞计数来评估肺损伤。支气管肺泡灌洗液中LPS-1/R组的总蛋白浓度为59.48 ± 14.87 μ g/ml（n = 11），VEH-1/R组的总蛋白浓度为239.41 ± 60.12 μ g/ml（n = 16）（P < 0.05）。来自LPS-LPS、VEH-LPS和SHAM的BAL液蛋白含量分别为63.49 +/- 8.10 μ g/ml（n = 7）、81.71 +/- 10.14 μ g/ml（n = 7）和33.02 +/- 12.22 μ g/ml（n = 8），并且彼此没有显著差异。各组BALF液细胞计数和BALF蛋白水平。这些数据表明，用LPS预处理增加响应于I/R的TNF释放，但保护随后的肺损伤。此外，通过定量血清AST评估该模型中的肝损伤。在肝I/R前用LPS预处理的动物中，没有证据表明肝缺血/再灌注后的肝损伤有差异。(C)1994年出版社出版。
In vivo administration of nonlethal doses of lipopolysaccharide (LPS) to rodents can result in protection from subsequent lethal doses of endotoxin or LPS. We have previously demonstrated that hepatic ischemia/ reperfusion (I/R) results in a TNF-dependent lung and liver injury and we postulated that pretreatment with sublethal concentrations of LPS prior to hepatic IIR could be protective from this injury. To test this hypothesis, five groups of rats were studied. LPS-I/R received 25 mu g of LPS iv 24 hr prior to I/R, VEH-I/R received an equivalent volume of vehicle iv 24 hr prior to I/R, LPS-LPS received 25 mu g of LPS iv 24 hr prior to sham laparotomy at which time an additional 25 mu g of LPS was given iv, VEH-LPS received an equivalent volume of vehicle 24 hr prior to sham laparotomy and 25 mu g of LPS iv immediately prior to sham laparotomy, and SHAM consisted of sham-operated control animals. Peak plasma tumor necrosis factor-cu (TNF) levels occurred between 30 and 150 min of reperfusion: LPS-I/ R = 778 +/- 150 pg/ml (n = 5), VEH-I/R = 145 +/- 46 pg/ml (n = 5), LPS-LPS = 970 +/- 716 pg/ml (n = 4), VEH-LPS = 15,949 +/- 10,937 (n = 5), and SHAM = 3 +/- 1 (n = 5). As previously demonstrated by other investigators, pretreatment with LPS decreases TNF release in response to a second dose of LPS; however, TNF release was increased following hepatic I/R in those animals pretreated with LPS (LPS-I/R vs VEH-I/R, P = 0.014). Pulmonary injury was assessed by total protein and cell counts in bronchoalveolar lavage (BAL) fluid. Total protein concentration in BAL fluid from LPS-I/R = 59.48 +/- 14.87 mu g/ml (n = 11) and from VEH-I/R = 239.41 +/- 60.12 mu g/ml (n = 16) (P < 0.05). BAL fluid protein contents from LPS-LPS, VEH-LPS, and SHAM were 63.49 +/- 8.10 mu g/ml (n = 7), 81.71 +/- 10.14 mu g/ml (n = 7), and 33.02 +/- 12.22 mu g/ml (n = 8), respectively, and were not significantly different from each other. BAL fluid cell counts paralleled protein levels in each group. These data suggest that pretreatment with LPS increases TNF release in response to I/R, but protects from the subsequent pulmonary injury. In addition, liver injury in this model was assessed by quantitation of serum AST. There was no evidence of a difference in the liver injury which followed hepatic ischemia/reperfusion in animals which were pretreated with LPS before hepatic I/R. (C) 1994 Academic Press, Inc.