高渗氯化钠羟乙基淀粉溶液对未控制出血性休克大鼠心肌损伤的影响

Effect of hypertonic sodium chloride hydroxyethyl starch 40 on myocardial injury induced by uncontrolled hemorrhagic shock in rats

目的观察高渗氯化钠羟乙基淀粉溶液(hypertonic sodium chloride hydroxyethyl starch 40,HHS)对未控制出血性休克(uncontrolled hemorrhagic shock,UHS)大鼠心肌损伤的保护作用并探讨其可能机制。方法采用修订的Capone等方法制备创伤UHS模型。用随机数字表法将30只SD大鼠分为3组(n=10):正常对照组(NC组)、生理盐水复苏组(NS组)、高渗氯化钠羟乙基淀粉溶液复苏组(HHS组)。NS组及HHS组大鼠经动脉放血,使血压降至40 mmHg,然后断尾75%,造成活动性出血。分别给予生理盐水(NS)和HHS输注,使MAP维持在50 mmHg。复苏1后,两复苏组均给予手术止血、回输血液及给予足量的液体输注,保持MAP 0 mmHg。持续监测左心室收缩压(LVSP)、左室压力最大上升及下降速率(±dp/dt max)及左室舒张末压(LVEDP);分别于伤后0(T0)、30(T1)、90(T2)、210(T3)min测定肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)的活性及肌钙蛋白I(cTnI)浓度;观察实验结束时心肌组织超微结构改变;于T3时点处死大鼠,制备心肌组织匀浆,检测MDA、SOD、TNF-α及IL-6水平;经TUNEL染色观察心肌细胞凋亡情况。结果 HHS组复苏后心功能指标较NS组明显升高(P<0.05);HHS组CK-MB、LDH活性及cTnI浓度明显低于NS组(P<0.05);HHS组心肌组织超微结构损伤比NS组明显减轻;HHS组心肌匀浆MDA、TNF-α及IL-6浓度均显著低于CON组,心肌匀浆SOD活性显著高于CON组(P<0.05);HHS组大鼠心肌细胞凋亡率明显低于NS组(P<0.05)。结论 HHS对UHS大鼠心肌有保护作用;减少氧自由基释放和SOD消耗,降低炎症因子的产生以及抑制心肌细胞凋亡可能是其中的机制。

Objective To study the protective effect of hypertonic sodium chloride hydroxyethyl starch 40 （HHS） on myocardial injury in rats with uncontrolled hemorrhagic shock （UHS） and the possible mechanisms. Methods Rat models of UHS were established using the modified Capone method. Thirty SD rats were randomly divided into a normal control （NC） group, a normal saline （NS） group, and a HHS group （n=10）. The blood pressure of rats in the NS group and HHS group was decreased to 40 mmHg by artery bloodletting, and then active hemorrhage was induced by 75% tail amputation. The rats were given NS and HHS infusion to maintain the MAP at 50 mmHg. In 1 h after resuscitation, the rats underwent operation for hemostasis followed by blood and sufficient fluid transfusion to maintain the MAP at 90 mmHg. Cardiac function indices including left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP） and dp/dtmax were monitored continuously during the time of UHS and resuscitation. Arterial blood samples were taken at 0 （T0）, 30 （T1）, 90 （T2） and 210 min （T3） after UHS for determination of the levels of creatine kinase isoenzyme MB （CK-MB）, lactate dehydrogenase （LDH） and cardiac troponin I （cTnI）. Myocardium samples of rats were extracted for observation of ultrastructural changes under an electron microscope. All the rats were sacrificed and the heart was made for tissue homogenate to determine the levels of malondialdehyde （MDA）, superoxide dismutase （SOD）, tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） at T3. Myocardial apoptosis was detected by TUNEL staining. Results The cardiac function indices were significantly improved in the HHS group than in the NS group （P〈0.05）. Compared with the NS group, the levels of CK-MB, LDH and cTnI significantly decreased in the HHS group （P〈0.05）. There were less ultrastructural changes of myocardium in the HHS group than in the NS group. The levels of MDA, TNF-α and IL-6 in the myocardium of the HHS group were significantly lower than those of the NS group, while the SOD activity was significantly higher in the HHS group than in the NS group （P〈0.05）. The myocardial apoptosis significantly decreased in the HHS group compared with the NS group （P〈0.05）. Conclusion HHS can reduce myocardial injury induced by UHS in rats. The myocardial protection of HHS is probably mediated by reducing the release of free radical and consumption of SOD, decreasing the generation of TNF-α and IL-6, and inhibiting myocardial apoptosis.