[Abstract] Objective To explore the protective effects of Ulinastatin for the septic patients with renal injury to analyze the influence on the prognosis and immune function and to investigate its possible mechanism and provide the basis for clinical therapy Methods Forty six patients with sepsis were selected in the People's Hospital of Lishui City from March 2010 to February 2014 They were randomly divided into the control group (22 cases) who were treated with conventional treatment and nursing and the observation group (24 cases) were treated with Ulinastatin on the basis of conventional therapy The blood urea nitrogen (BUN) and serum creatinine (SCr) and Cystatin C (Cystatin C) T cell subsets were evaluated the serum tumor necrosis factorα (TNFα) and interleukin 6 (IL6) level and acute physiology and chronic health evaluation (APACHE Ⅱ) scores before and after treatment were detected Results Cystatin C BUN and SCr of two groups after treatment were obviously lower than those before treatment the differences were statistically significant (P < 005) Cystatin C BUN and SCr of the observation group after treatment were (121±024) mgL (1492±123) mmolL and (21074±1836) μmolL
lower than the control group after treatment [(157±016) mgL (1612±104) mmolL and (25433±2382) μmolL] (P < 005) Compared to before treatment CD4+ CD8+ and CD4+CD8+ of two groups the differences were statistically significant (P < 005) CD4+ and CD4+CD8+ of the observation group after treatment was (4387±504) and (182±029) higher than that of the control group after treatment [(3804±451) and (130±037)] (P < 005) CD8+ of the observation group after treatment was (3192±326) lower than the control group after treatment [(3542±311)] (P < 005) TNFα and IL6 of two groups after treatment compared with before treatment the difference was statistically significant (P < 005) TNFα and IL6 of the observation group after treatment were (20166±1744) (17354±158) ngL lower than the control group after treatment [(23685±1951) (21796±2032) ngL] there was a significant difference (P < 005) APACHE Ⅱ score of the observation group after treatment was (1560±123) scores lower than the control group after treatment [(1924±165) scores] and the two groups after treatment were lower than those before treatment (P < 005) Conclusion There is better protective of Ulinastatin on septic renal injury which can obviously improve the immune function
reduce the inflammatory factor and it is worthy of clinical application [Key words] Ulinastatin Sepsis Renal injury Immune function
脓毒症感染创伤休克等床急危重症患者严重发症感染致全身炎性反应综合征诱发脓毒性休克器官功障碍综合征重原脓毒血症患者病情通常十分危重常伴肺肾脏等脏器功衰竭患者死亡率较高床危重症急救医学中重难题[12]国外研究认机体炎症反应免疫功紊乱脓毒症发生发展重环节时效阻断失控炎症反应提高机体免疫功治疗脓毒症重点乌司丁种广谱蛋白酶抑制剂够稳定溶酶体膜抑制炎症子释放具改善机体免疫功等特点常治疗急性胰腺炎慢性复发性胰腺炎急性循环衰竭抢救辅助药[34]研究旨探讨乌司丁脓毒症肾损伤保护作分析预免疫功影响探讨作机制床治疗预防脓毒血症提供客观
1 资料方法
11 般资料
选择2010年3月~2014年2月浙江省丽水市民医院收治脓毒症患者患者46例入选患者均符合严重sepsissepsis shock诊断标准(ACCPSCCM标准2001年华盛顿标准)[56]患者均≥18岁APACHEⅡ评分≥12分机患者分组观察组中组22例男女11例均年龄(4612±308)岁APACHEⅡ评分(1933±294)分观察组24例男13例女11例均年龄(4538±264)岁APACHE
Ⅱ评分(1940±321)分两组患者性年龄APACHEⅡ等基资料方面较差异统计学意义(P > 005)具性排病例:治疗未超24 h死亡出院者6月接受化疗者3月接受皮质激素免疫抑制剂免疫调节剂治疗者免疫系统肾脏疾病患者
12 方法
患者均予重症监护抗感染营养支持呼吸机辅助呼吸等常规综合治疗护理观察组常规综合治疗基础予乌司丁治疗[常山生化药业(江苏)限公司批准文号:国药准字H20080367]次100 000单位溶5~10 mL氯化钠注射液中3次d缓慢静脉推注1周1疗程患者均治疗患者症状体征缓解出院死亡
13 观察指标
采集患者外周静脉血标检测治疗前尿素氮(BUN)血肌酐(SCr)胱抑素C(Cystatin C)含量等肾脏指标T细胞亚群结果评估患者治疗前急性生理慢性健康评分(APACHEⅡ评分)治疗前治疗应酶联免疫吸附测定(ELISA)方法检测血清中肿瘤坏死子α(TNFα)白细胞介素6(IL6)水
14 统计学方法
采SPSS 150软件计量资料采均数±标准差(x±s)表示采t检验P < 005差异统计学意义
2 结果
21 两组治疗前肾功指标结果较
次研究结果显示治疗前两组患者SCrBUNCystatin C结果较差异统计学意义(P > 005)两组患者治疗Cystatin CBUNSCr均低治疗前差异均统计学意义(P < 005)观察组患者治疗Cystatin CBUNSCr均低组患者治疗差异均统计学意义(P < 005)见表1
22 两组治疗前T细胞亚群变化结果较
次研究结果显示治疗前两组患者CD4+CD8+CD4+CD8+结果较差异统计学意义(P > 005)两组患者治疗CD4+CD8+CD4+CD8+治疗前较差异均统计学意义(P < 005)观察组患者治疗CD4+CD4+CD8+均高组治疗差异统计学意义(P < 005)观察组患者治疗CD8+低组治疗差异统计学意义(P < 005)见表2
23 两组治疗前TNFαIL6结果较
次研究结果显示治疗前两组患者TNFαIL6结果较差异统计学意义(P > 005)两组患者治疗TNFαIL6治疗前较差异均统计学意义(P < 005)观察组患者治疗TNFαIL6均低组治疗差异统计学意义(P < 005)见表3
表3 两组治疗前TNFαIL6结果较(ngLx±s)
注:组治疗较△P < 005组治疗前较▲P < 005TNFα:肿瘤坏死子αIL6:白细胞介素6
24 两组治疗前APACHEⅡ评分结果较
次研究结果显示组治疗前APACHEⅡ评分(2538±179)分观察组治疗前(2515±172)分差异统计学意义(P > 005)观察组治疗APACHEⅡ评分(1560±123)分低组治疗[(1924±165)分]两组治疗均低治疗前差异均统计学意义(P < 005)
3 讨
脓毒血症感染引起全身炎性反应综合征病情危重导致器官功衰竭(MODS)床常急性肾损伤肾衰竭常见死亡率非常高[79]研究认脓毒症时肾损伤炎症介质度释放肾脏缺血灌注损伤导致肾脏细胞凋亡乌司丁尿中提取蛋白水解酶抑制剂种蛋白酶类抑制作[10]年研究表明乌司丁具拮抗清炎症子作防止MODS发生发展抑制心肌抑制子产生改善休克时循环状态溶酶体膜具稳定作抑制炎症介质度释放清氧基等功[1112] 脓毒症患者机体巨噬细胞等炎性细胞细菌毒素刺激产生TNFαIL6等炎症子炎症子影响中性粒细胞释放蛋白酶水解酶等进引起肾肺等重器官损伤甚出现MODS床治疗脓毒症需控制炎症反应调控机体免疫功机体处免疫稳定状态BUN体蛋白质代谢终末产物急慢性肾功衰竭等肾脏损伤均血BUN增高SCr机体肌肉代谢产物床常解肾功方法Cystatin C分子量血浆蛋白结合通肾球滤膜肾球滤端肾全部重吸收分解肾球滤率密切相关理想反映肾球滤功源性标志物够较短时间评估肾脏状况[1314]次调查结果显示观察组组治疗BUNSCrCystatin
C均低治疗前差异统计学意义(P < 005)提示两组治疗均改善患者肾脏功观察组治疗BUNSCrCystatin C均低组治疗差异统计学意义(P < 005)提示乌司丁脓毒症肾损伤保护作更加明显乌司丁作Kunitz 型丝氨酸蛋白水解酶抑制剂种水解酶活性够起抑制作降低种水解酶机体正常组织器官损伤够稳定溶酶体膜抑制减少量超氧化物产生消产生超氧化物研究结果见观察组患者治疗TNFαIL6均低组治疗差异统计学意义(P < 005)提示乌司丁抑制炎性介质释放利休克时循环状态改善干扰心肌抑制子产生进促进肾脏功恢复[1516]常规治疗基础应乌司丁环节抑制细胞损伤保护患者重脏器改善患者环境清肾脏产生毒素效改善脓毒血症引起肾脏损伤
脓毒血症患者机体免疫反应发生障碍效清病原体导致机体免疫功紊乱作体免疫系统重调节细胞T细胞出现功失调方面致炎子减少抗炎子明显增炎症介质抗炎反应方倾斜方面患者出现免疫力麻痹机体T细胞特异性抗原刺激出现免疫弱反应甚反应性T淋巴细胞细胞免疫中免疫细胞仅参特异性免疫反应调节细胞免疫反应体液免疫应答[1718]次调查结果显示次结果显示两组治疗CD4+CD8+CD4+CD8+治疗前较差异均统计学意义(P < 005)提示两组治疗患者免疫功均明显提高时研究结果证实观察组治疗免疫功明显高组治疗差异统计学意义(P < 005)说明常规治疗基础应乌司丁治疗脓毒症肾损伤调节患者机体免疫功进提高肾脏保护作减轻肾脏损伤方面乌司丁调节T淋巴细胞亚群稳定免疫功通改善微循环组织灌注改善患者微循环减轻局部组织缺氧缺血恢复免疫功[1920]观察组组治疗APACHEⅡ评分结果见两组均低治疗前观察组治疗APACHE
Ⅱ评分低组差异统计学意义(P < 005)提示两组均效治疗脓毒症肾损伤具保护作进步证实乌司丁利脓毒症患者肾脏保护治疗减低肾脏损害程度
综述乌司丁脓毒症肾损伤具保护作够显著改善患者免疫功降低炎性子值床推广应
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