摘要
目的对拟通过肝血流阻断切除肿瘤的患者预先给予血必净注射液，观察其对术后可能发生的缺血，再灌注（I/R）损伤及凝血功能紊乱的保护作用。方法采用前瞻性随机对照研究，收集2011年10月至2013年3月中山大学肿瘤防治中心肝胆科收治的拟行肝癌切除术、肝功能Child—Pugh分级均为A级的60例患者，按随机数余数法分为对照组和血必净组（术前连续3d静脉滴注血必净注射液，每次100mL加入0．9％生理盐水注射液中进行预处理），于手术前后测定血常规、凝血功能、肝功能、血清炎症细胞因子及甲胎蛋白（AFP）等水平。结果最终纳入45例患者，对照组23例，血必净组22例；43例患者为慢性乙型病毒性肝炎。与手术前比较，两组手术后丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）明显升高，凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）明显延长，白细胞计数（WBC）、中性粒细胞比例（N）、C-反应蛋白（CRP）明显升高（P〈0．05或P〈0．01）；血必净组手术后以上指标不同程度地低于对照组[ALT（U/L）：213．1（80．4—796．6）比265．8（15．6—882．3），AST（U／L）：194．1（65．4～914．2）比264．3（15．4～475．9），LDH（1g，U／L）：5．69±0．72比5．71±0．72，PT（s）：15．24±2．16比14．41±1．33，APTT（s）：31．51±7．04比29．47±4．90，WBC（×10^9／L）：13．47±4．66比14．58±4．40，N：0．87±0．06比0．87±0．04，CRP（mg／L）：40．64（16．93～189．59）比45．64（11．65～349．40）]，但差异均无统计学意义（均P〉0．05）。两组手术前肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）均低于1．0ng／L；手术后对照组和血必净组TNF—α水平均无明显变化，IL-6分别升高至485．10（104．00～837．50）n#L、193．26（95．10～385．20）ng／L（两组比较P〈0．01）。两组手术后高迁移率族蛋白B1（HMGB1）水平均明显高于手术前（均P〈0．01），血必净组手术后HMGB1水平明显低于对照组（μg/L：268．73±5．56比277．12±2．92，P〈0．01）。血必净组急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分明显低于对照组（分：4．18±3．75比4．53±2．34，t=5．328，P=0．027），术后首次排气、排便时间均明显早于对照组[排气时间（d）：3（2～4）比3（2～4），u=-2．023，P=0．043；排便时间（d）：4（2-6）比5（3-8），u=-2．926，P=0．003]，但术后住院天数和总住院天数比较差异无统计学意义。Spearman秩相关分析显示，乙型肝炎病毒基因（HBV～DNA）阳性的33例患者HBV—DNA水平与术前ALT（r=0．414，P=0．044）、AST（r=0．405，P=0．024）呈明显正相关，与手术前后其他肝功能指标均无明显相关性。结论入肝血流阻断肝癌切除术可造成一定程度的肝I／R损伤及凝血功能紊乱；血必净注射液可能通过抑制肝脏I／R后炎症因子的释放，减轻肝组织损伤，且对患者术后肠道功能恢复具有促进作用，但对改善凝血功能紊乱的作用不明显。
Objective To observe the protective effect of Xuebijing injection pretreatment on hepatic ischemia/reperfusion （I/R） injury and coagulopathy in liver cancer patients undergoing excision of hepatic cancer after occlusion of hepatic blood flow. Methods A prospective randomly controlled study was conducted. Sixty patients with liver cancer classified as Child-Pugh class A undergoing hepatectomy in the Department of Hepatobiliary Surgery of Sun Yat-sen University Cancer Center from October 2011 to March 2013 were enrolled. The patients were randomized into control group and Xuebijing group （each patient received 100 mL Xuebijing injection added to 0.9% saline as a preoperative treatment for 3 days）. Complete blood count, coagulation function, hepatic function, serum pro-inflammatory cytokines and alpha-fetoprotein （AFP） levels were determined before and after operation. Results Forty-five out of 60 patients were enrolled eventually, with 23 patients in control group and 22 in Xuebijing group, and among them 43 patients were positive for hepatitis B surface antigen （HBsAg） at admission. Compared with those before operation, the postoperative levels of alanine transaminase （ALT）, aspartate transaminase （AST） and lactate dehydrogenase （LDH） in control and Xuebijing groups were significantly elevated, prothrombin time （PT） and activated partial prothrombin time （APTT） were significantly prolonged, and white blood cells （WBC）, proportion of neutrophils （N） and C-reactive protein （CRP） were significantly increased （P〈0.05 or P〈0.01 ）. Although the above indexes in Xuebijing group after operation were lower than those in control group in different degrees [ALT （U/L）： 213.1 （80.4-796.6） vs. 265.8 （15.6-882.3）, AST （U/L）： 194.1 （65.4-914.2） vs. 264.3 （15.4-475.9）, LDH （Ig,U/L）： 5.69 ± 0.72 vs. 5.71 ± 0.72, PT （s）： 15.24 ± 2.16 vs. 14.41 ± 1.33, APTP （s） ： 31.51 ± 7.04 vs. 29.47 ± 4.90, WBC （ × 10^9/L）： 13.47±4.66vs. 14.58±4.40, N： 0.87±0.06vs. 0.87±0.04, CRP （mg/L）： 40.64 （16.93-189.59）vs. 45.64 （11.65-349.40） ] no statistical significance was found between the groups （all P〉0.05 ）. The preoperative levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were both less than 1.0 ng/L, and the postoperative levels of TNF-α showed no significant change, and IL-6 was increased to 485.10 （104.00-837.50） ng/L and 193.26 （95.10-385.20） ng/L in control and Xuebijing groups respectively （P〈0.01）. The serum high mobility group box-1 （HMGB 1 ） protein levels after operation were higher than those of preoperative in both groups （both P〈 0.01 ）, but the postoperative HMGBI in Xuebijing group were significantly lower than those in control group （ μg/L： 268.73 ± 5.56 vs. 277.12 ± 2.92, P〈0.01 ）. Acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ ）score in Xuebijing group was significantly lower than that in control group （4.18 ±3.75 vs. 4.53 ±2.34, t=5.328, P=0.027）, and the first passage of flatus and defecation after operation in Xuebijing group were significantly earlier than those in control group [exhaust time （days）： 3 （2-4） vs. 3 （2-4）, U=-2.023, P=0.043; defecation time （days）： 4 （2-6） vs. 5 （3-8）, U=-2.926, P=0.0033. However, no difference was found between two groups in the Postoperative and total hospital days. Spearman rank correlation analysis showed there were positive correlations between hepatitis B virus （HBV）-DNA levels and preoperative ALT （r=0.414, P=0.044） and AST （r=0.405, P=0.024） in 33 HBV-DNA positive patients, but there was no significant correlation between HBV-DNA levels or other preoperative liver function indicators. Conclusions Hepatic I/R injury and coagulopathy may occur in liver cancer patients undergoing resection of cancer with occlusion of hepatic blood flow. Xuebijing injection may inhibit The release of serum pro-inflammatory cytokines, thereby alleviate hepatic I/R injury and promote the recovery of intestinal, function. But it does not offer protective effect on coagulopathy.
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2013年第12期743-748,共6页
Chinese Critical Care Medicine
基金
卫生部医药卫生科技发展研究项目（WH2011-01-02）
关键词
血必净注射液
肝癌
肝切除术
缺血
再灌注损伤
凝血功能
细胞因子
Xuebijing injection
Liver cancer
Hepatectomy
Ischemia/reperfusion injury
Coagulation function
Cytokine
