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100 mL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(lg,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(×109/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1.0 ng/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)ng/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.
目的 對擬通過肝血流阻斷切除腫瘤的患者預先給予血必淨註射液,觀察其對術後可能髮生的缺血/再灌註(I/R)損傷及凝血功能紊亂的保護作用.方法 採用前瞻性隨機對照研究,收集2011年10月至2013年3月中山大學腫瘤防治中心肝膽科收治的擬行肝癌切除術、肝功能Child-Pugh分級均為A級的60例患者,按隨機數餘數法分為對照組和血必淨組(術前連續3d靜脈滴註血必淨註射液,每次100 mL加入0.9％生理鹽水註射液中進行預處理),于手術前後測定血常規、凝血功能、肝功能、血清炎癥細胞因子及甲胎蛋白(AFP)等水平.結果 最終納入45例患者,對照組23例,血必淨組22例;43例患者為慢性乙型病毒性肝炎.與手術前比較,兩組手術後丙氨痠轉氨酶(ALT)、天鼕氨痠轉氨酶(AST)、乳痠脫氫酶(LDH)明顯升高,凝血酶原時間(PT)、活化部分凝血活酶時間(APTT)明顯延長,白細胞計數(WBC)、中性粒細胞比例(N)、C-反應蛋白(CRP)明顯升高(P＜0.05或P＜0.01);血必淨組手術後以上指標不同程度地低于對照組[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(lg,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(×109/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)],但差異均無統計學意義(均P＞0.05).兩組手術前腫瘤壞死因子-α(TNF-α)、白細胞介素-6(IL-6)均低于1.0 ng/L;手術後對照組和血必淨組TNF-α水平均無明顯變化,IL-6分彆升高至485.10(104.00～837.50)ng/L、193.26(95.10～ 385.20) ng/L(兩組比較P＜0.01).兩組手術後高遷移率族蛋白B1(HMGB1)水平均明顯高于手術前(均P＜0.01),血必淨組手術後HMGB1水平明顯低于對照組(μg/L:268.73±5.56比277.12±2.92,P＜0.01).血必淨組急性生理學與慢性健康狀況評分繫統Ⅱ(APACHEⅡ)評分明顯低于對照組(分:4.18±3.75比4.53±2.34,t=5.328,P=0.027),術後首次排氣、排便時間均明顯早于對照組[排氣時間(d):3(2～4)比3(2～4),U=-2.023,P=0.043;排便時間(d):4(2～6)比5(3～8),U=-2.926,P=0.003],但術後住院天數和總住院天數比較差異無統計學意義.Spearman秩相關分析顯示,乙型肝炎病毒基因(HBV-DNA)暘性的33例患者HBV-DNA水平與術前ALT(r=0.414,P=0.044)、AST(r=0.405,P=0.024)呈明顯正相關,與手術前後其他肝功能指標均無明顯相關性.結論 入肝血流阻斷肝癌切除術可造成一定程度的肝I/R損傷及凝血功能紊亂;血必淨註射液可能通過抑製肝髒I/R後炎癥因子的釋放,減輕肝組織損傷,且對患者術後腸道功能恢複具有促進作用,但對改善凝血功能紊亂的作用不明顯.
목적 대의통과간혈류조단절제종류적환자예선급여혈필정주사액,관찰기대술후가능발생적결혈/재관주(I/R)손상급응혈공능문란적보호작용.방법 채용전첨성수궤대조연구,수집2011년10월지2013년3월중산대학종류방치중심간담과수치적의행간암절제술、간공능Child-Pugh분급균위A급적60례환자,안수궤수여수법분위대조조화혈필정조(술전련속3d정맥적주혈필정주사액,매차100 mL가입0.9％생리염수주사액중진행예처리),우수술전후측정혈상규、응혈공능、간공능、혈청염증세포인자급갑태단백(AFP)등수평.결과 최종납입45례환자,대조조23례,혈필정조22례;43례환자위만성을형병독성간염.여수술전비교,량조수술후병안산전안매(ALT)、천동안산전안매(AST)、유산탈경매(LDH)명현승고,응혈매원시간(PT)、활화부분응혈활매시간(APTT)명현연장,백세포계수(WBC)、중성립세포비례(N)、C-반응단백(CRP)명현승고(P＜0.05혹P＜0.01);혈필정조수술후이상지표불동정도지저우대조조[ALT(U/L):213.1(80.4～796.6)비265.8(15.6～882.3),AST(U/L):194.1 (65.4～914.2)비264.3(15.4～475.9),LDH(lg,U/L):5.69±0.72비5.71±0.72,PT(s):15.24±2.16비14.41±1.33,APTT(s):31.51±7.04비29.47±4.90,WBC(×109/L):13.47±4.66비14.58±4.40,N:0.87±0.06비0.87±0.04,CRP(mg/L):40.64(16.93 ～ 189.59)비45.64(11.65 ～ 349.40)],단차이균무통계학의의(균P＞0.05).량조수술전종류배사인자-α(TNF-α)、백세포개소-6(IL-6)균저우1.0 ng/L;수술후대조조화혈필정조TNF-α수평균무명현변화,IL-6분별승고지485.10(104.00～837.50)ng/L、193.26(95.10～ 385.20) ng/L(량조비교P＜0.01).량조수술후고천이솔족단백B1(HMGB1)수평균명현고우수술전(균P＜0.01),혈필정조수술후HMGB1수평명현저우대조조(μg/L:268.73±5.56비277.12±2.92,P＜0.01).혈필정조급성생이학여만성건강상황평분계통Ⅱ(APACHEⅡ)평분명현저우대조조(분:4.18±3.75비4.53±2.34,t=5.328,P=0.027),술후수차배기、배편시간균명현조우대조조[배기시간(d):3(2～4)비3(2～4),U=-2.023,P=0.043;배편시간(d):4(2～6)비5(3～8),U=-2.926,P=0.003],단술후주원천수화총주원천수비교차이무통계학의의.Spearman질상관분석현시,을형간염병독기인(HBV-DNA)양성적33례환자HBV-DNA수평여술전ALT(r=0.414,P=0.044)、AST(r=0.405,P=0.024)정명현정상관,여수술전후기타간공능지표균무명현상관성.결론 입간혈류조단간암절제술가조성일정정도적간I/R손상급응혈공능문란;혈필정주사액가능통과억제간장I/R후염증인자적석방,감경간조직손상,차대환자술후장도공능회복구유촉진작용,단대개선응혈공능문란적작용불명현.
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 (lg,U/L):5.69 ± 0.72 vs.5.71 ± 0.72,PT (s):15.24 ± 2.16 vs.14.41 ± 1.33,APTT (s):31.51 ± 7.04 vs.29.47 ± 4.90,WBC (× 109/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 HMGB1 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=0.003].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 coagnlopathy 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.
