卡巴胆碱对脓毒症大鼠内脏组织缺血引起脂质过氧化损伤的作用研究

The protective effects of carbachol on visceral ischemia-induced lipid peroxidation injury in rats with sepsis

目的探讨卡巴胆碱（CAR）对脓毒症大鼠脏器组织灌流和脂质过氧化损伤的影响。方法雄性SD大鼠64只，采用盲肠结扎穿孔术（CLP）制备大鼠脓毒症模型。随机分为CAR处理组和CLP组，每组32只，术后即刻两组分别静脉注射CAR10ug／kg或等量生理盐水。每组16只用于观察12h和24h死亡率；其余16只于CLP后18h测定平均动脉压（MAP）和肝、肾、空肠组织血流量；取血测定血浆丙氨酸转氨酶（ALT）和肌酐（Cr）水平；后处死动物，测定空肠组织二胺氧化酶（DAO）活性及肝、肾、空肠组织黄嘌呤氧化酶（XOD）活性、丙二醛（MDA）含量和组织含水量。结果CAR组12h和24h死亡率分别为25．0％（4／16）和50．0％（8／16），显著低于CLP组[37．5％（6／16），75．0％（12／16），P均〈0．05]。CLP后18h，两组MAP差异无统计学意义（P〉0．05）；CAR组肝、肾、空肠组织血流量均明显大于CLP组（P均〈0．05），肾和空肠组织XOD活性、MDA含量及组织含水量显著低于CLP组（P均〈0．05）；脏器功能指标[ALT：（64．3±8．3）U／L，Cr：（96．4±7．0）umol／L，DAO：（0．20±0．04）U／L]的改善程度也均显著优于CLP组（ALT：（81．5±7．9）U／L，Cr：（117．1±6．7）umol／L，DAO：（0．12±0．03）U／L，P均〈0．053。结论CAR能改善脓毒症大鼠内脏灌流、抑制氧自由基生成，减轻组织水肿和脏器功能损害。

Objective To investigate the effect of carbachol （CAR） on visceral perfusion and lipid oxidation injury in rats with sepsis. Methods Sixty-four Sprague-Dawley （SD） rats received cecal ligation and puncture （CLP） surgery, and they were divided randomly into two groups： septic model group （CLP group, n= 32） and septic model with CAR-treatment group （CAR group, n= 32）. CAR （10ug/kg, CAR group） or normal saline （CLP group） was immediately injected into penial vein. Sixteen animals in each group were used to observe the mortality rates 12 hours and 24 hours after CLP, and the remaining rats for measurement of variables of blood and tissue. At the 18 hours after CLP, the mean arterial pressure （MAP）, the blood flow （BF） of liver, kidney and jejunum, the plasma levels of alanine aminotransferase （ALT） and creatinine （Cr） were measured. Animals were sacrificed after the aforementioned determinations, and specimens of liver, kidney and jejunum were harvested for evaluation of malondialdehyde （MDA）, xanthine oxidase （XOD）, and assessment of tissue water content （ratio of dry to wet weight） of those organs. The activity of diamine oxidase （DAO） in jejunal tissue was detected. Results The mortality rates of 12 hours and 24 hours of CAR group were 25.0% （4/16）and 50. 0% （8/16） respectively, all significantly lower than those of CLP group [37.5% （6/16） and 75% （12/16）, both P〈0.05]. CAR treatment did not result in significant statistical difference in the levels of MAP compared with CLP group at 18 hours after CLP （P〉0.05）, but led to significant increases in BF of CAR group in liver, kidney and jejunum compared with those of CLP group （all P〈0. 05）. The levels of XOD and MDA, as well as the tissue water content were significantly lower in CAR group than CLP group in kidney and jejunum （all P〈0.05）. The parameters of organ function were significantly different in CAR group compared with CLP group [ALT： （64.3 ± 8.3） U/L vs. （81.5±7.9） U/L, Cr： （96.4±7.0） umol/L vs. （117.1±6.7） umol/L, DAO：（0.20±0.04） U/L vs. （0.12±0.03） U/L, all P〈0.05]. Conclusion The results indicate that CAR promotes visceral perfusion, inhibits lipid peroxidation production and alleviates visceral edema and dysfunction in rats with sepsis.