维生素C在脓毒症中的应用进展

脓毒症是重症患者发病和死亡的主要原因。由于氧化应激时代谢消耗增加以及脱氢抗坏血酸再循环减少等原因,脓毒症患者常合并维生素C减少或缺乏。外源性补充维生素C,可能是脓毒症有效的辅助治疗措施。本文就维生素C在脓毒症中应用的作用机制、用法用量、潜在副作用、联合疗法及目前开展的临床研究等方面进行综述,旨在深化临床医师对维生素C在脓毒症治疗中的作用的认识。     

肥大细胞在脓毒症中的作用研究进展

脓毒症是机体对感染的失控反应所导致可以威胁生命的器官功能障碍。组织肥大细胞（mast cell,MC）作为炎症反应的经典效应细胞之一,由血液肥大细胞前体细胞发育而来,可通过分泌多种炎症介质和细胞因子,从而在脓毒症发生发展中发挥重要作用。我们对MC在脓毒症中的潜在作用做一总结,为探索MC在脓毒症中的新机制提供新思路。     

蛋白C系统与脓毒症

蛋白 C(protein C,PC)系统是体内抗凝的主要成分之一〔1 ,2〕。 PC在体内为一种维生素 K依赖性丝氨酸蛋白酶原 ,受凝血酶凝血酶调节蛋白 (thrombinthrombomodulin,T TM)复合物激活为活性 PC (activated protein C,APC ) ,灭活凝血因子 a、 a而达到抗凝作用。近年来 ,随着脓毒症 (sepsis)病理生理的研究进展 ,PC在脓毒症治疗中的作用受到人们重视 ,并成为研究热点。1　脓毒症病因学的新认识近年来 ,感染、炎症、内环境的联系持续受到人们的重视 ,炎症级联和凝血级联及其相互作用可能是脓毒症预后的决定因素〔3,4〕。1.1　炎症级联 :…     

活化蛋白C与脓毒症

革蓝阴性、革蓝阳性细菌等感染引起脓毒症时 ,血管内皮细胞损伤 ,血栓调理素下调、机体激活蛋白Ｃ能力下降使活化蛋白Ｃ调节凝血酶的功能降低、微循环内发生凝血 ,造成ＤＩＣ ,引起急性器官功能衰竭 ,最终导致死亡。近年研究发现 ,活化蛋白Ｃ具有调节微循环凝血平衡、调节炎症功能 ,在体和离体研究显示重组活化蛋白Ｃ可通过多种机制抑制脓毒症中的炎症和促凝血反应。1.蛋白Ｃ系统的组成和功能　蛋白Ｃ系统是体内天然抗凝系统 ,由蛋白Ｃ、蛋白Ｓ、血栓调理素及因子Ｖ组成[1 ] 。蛋白Ｃ活化后表现丝氨酸蛋白酶活性 ,灭活Ⅴａ、Ⅷａ,发挥抗凝作…     

活化蛋白C与脓毒症

二十世纪后半叶,由于抗生素的应用使急性感染性疾病的发病率和死亡率都有所降低,但脓毒症的发生率仍有上升。据美国流行病学专家统计,近二十年来脓毒症发生率由82·7/10万人上升至240.4/10万人,全球死亡率为28%;在美国严重脓毒症的死亡率更高达30%~50%[1~3]。近年来的研究证实,凝血系统异常在脓毒症发生、发展过程中具有重要作用,其中蛋白C系统更是起到关键作用。1脓毒症的定义及发病机制1991年,美国胸科医师学会(ACCP)和危急医学学会(SC-CM)召开联席会议,把脓毒症定义为全身炎症反应综合征(systemic inflammatory response syndrome,S…     

血氨在急诊科脓毒症患者预后评估中的作用

目的:探究血氨在急诊科脓毒症患者预后评估中的应用,并与急诊脓毒症病死率评分（mortality in emergency department sepsis,MEDS)进行分析比较。方法:采用回顾性临床研究,纳入2017年6月至2018年5月期间于四川大学华西医院急诊科确诊的、符合2001年美国胸科医师协会／危重病医学会共识会议的诊断标准的脓毒症患者的临床资料,排除伴有其他影响血氨水平的疾病及失访的对象,并收集MEDS评分,电话随访统计患者的生存情况。采用独立样本 t检验比较两组间差异,应用受试者操作特性（ROC）曲线评估脓毒症病死率预测的准确性,使用logistic回归模型探讨血氨与MEDS评分联合应用的价值。 结果:最终纳入80例研究对象,按预后分为1周存活组（ n=52）、1周死亡组（ n=28）;4周存活组（ n=37）、4周死亡组（ n=43）;12周存活组（ n=33）、12周死亡组（ n=47）;1年存活组（ n=32）、1年死亡组（ n=48）,组间研究对象的人口特征差异无统计学意义,所有死亡对象的血氨水平均比同期存活的患者更高[（116.57±85.33）μmol/L vs （77.64±35.82）μmol/L,（108.53±73.00）μmol/L vs （71.19±32.53）μmol/L,（106.75±71.59）μmol/L vs （69.21±28.84）μmol/L,（105.77±71.14）μmol/L vs （69.50±29.25） μmol/L, P<0.05];根据1周、4周、12周和1年后的死亡情况得出,血氨的ROC曲线下面积(AUC)分别0.668（95% CI:0.542~0.793, P=0.014）、0.706（95% CI: 0.593~0.819, P=0.002）、0.705（95% CI: 0.592~0.818, P=0.002）、0.697（95% CI:0.582~0.811, P=0.003）;与单独使用血氨、乳酸或MEDS评分相比,血氨与MEDS的联合使用会提高对脓毒症患者预后评估的准确性（ P<0.05）。 结论:血氨用于预测急诊科脓毒症患者的近期和1年预后都具有较高的价值,与MEDS评分的联合使用,可以进一步提高其预测价值。     

重组人活化蛋白C在脓毒症中的应用

脓毒症(sepsis)是ICU常见的一种严重感染性疾病,来势凶猛,病情进展迅速,病死率高。在美国重度脓毒症死亡率30%～50%[1]。凝血异常与炎症是机体对感染的反应,严重脓毒症患者上述两种系统明显异常。活化蛋白C(activatedprotein C,APC)是近年来引起人们注意的人体内一种具有促纤维     

血氨在急诊科脓毒症患者预后评估中的作用

目的:探究血氨在急诊科脓毒症患者预后评估中的应用,并与急诊脓毒症病死率评分（mortality in emergency department sepsis,MEDS)进行分析比较。方法:采用回顾性临床研究,纳入2017年6月至2018年5月期间于四川大学华西医院急诊科确诊的、符合2001年美国胸科医师协会／危重病医学会共识会议的诊断标准的脓毒症患者的临床资料,排除伴有其他影响血氨水平的疾病及失访的对象,并收集MEDS评分,电话随访统计患者的生存情况。采用独立样本 t检验比较两组间差异,应用受试者操作特性（ROC）曲线评估脓毒症病死率预测的准确性,使用logistic回归模型探讨血氨与MEDS评分联合应用的价值。 结果:最终纳入80例研究对象,按预后分为1周存活组（ n=52）、1周死亡组（ n=28）;4周存活组（ n=37）、4周死亡组（ n=43）;12周存活组（ n=33）、12周死亡组（ n=47）;1年存活组（ n=32）、1年死亡组（ n=48）,组间研究对象的人口特征差异无统计学意义,所有死亡对象的血氨水平均比同期存活的患者更高[（116.57±85.33）μmol/L vs （77.64±35.82）μmol/L,（108.53±73.00）μmol/L vs （71.19±32.53）μmol/L,（106.75±71.59）μmol/L vs （69.21±28.84）μmol/L,（105.77±71.14）μmol/L vs （69.50±29.25） μmol/L, P<0.05];根据1周、4周、12周和1年后的死亡情况得出,血氨的ROC曲线下面积(AUC)分别0.668（95% CI:0.542~0.793, P=0.014）、0.706（95% CI: 0.593~0.819, P=0.002）、0.705（95% CI: 0.592~0.818, P=0.002）、0.697（95% CI:0.582~0.811, P=0.003）;与单独使用血氨、乳酸或MEDS评分相比,血氨与MEDS的联合使用会提高对脓毒症患者预后评估的准确性（ P<0.05）。 结论:血氨用于预测急诊科脓毒症患者的近期和1年预后都具有较高的价值,与MEDS评分的联合使用,可以进一步提高其预测价值。     

硫化氢在脓毒症大鼠心肌损伤中的作用

目的 研究硫化氢(H2S)在脓毒症大鼠心肌损伤中的作用.方法 雄性SD大鼠60只,月龄3～4个月,体质量180 ～220 g,随机(随机数字法)分为4组:对照组(Ⅰ组)、脓毒症组(Ⅱ组)、脓毒症+ NaHS(H2S供体)预处理组(Ⅲ组)、脓毒症+PAG(H2S代谢酶CSE抑制剂)组(Ⅳ组),每组各15只.采用盲肠结扎穿孔法制作脓毒症大鼠模型,观察各组大鼠血流动力学改变,测定心肌组织中H2S的变化,采用RT-PCR方法观察CSE mRNA表达,采用髓过氧化物酶(MPO)测定试剂盒测定各组心肌组织MPO含量,用ELISA方法检测心肌组织TNF-α、IL-1β的表达,光学显微镜下观察心肌形态学改变.结果 与Ⅰ组相比,Ⅱ组血压下降,心肌组织中H2S、TNF-α、IL-1β、MPO含量出现不同程度增加(P＜0.01或P＜0.05),CSE mRNA表达水平提高(P＜0.05);与Ⅱ组相比,Ⅲ组血压下降更为显著,心肌组织中H2S、TNF-α、IL-1β含量增加,MPO活性增强(P＜0.05),但CSE mRNA表达水平并无显著改变;与Ⅱ组相比,Ⅳ组血压水平接近,心肌组织中H2S、TNF-α、IL-1β 含量均降低,MPO活性减弱(P＜0.05),CSE mRNA表达水平下降(P＜0.05).四组心肌组织形态学损伤由轻到重依次为Ⅰ、Ⅳ、Ⅱ、Ⅲ.结论 脓毒症大鼠心肌组织CSE/H2S体系上调,给予H2S可以升高脓毒症大鼠心肌组织中MPO、TNF-α、IL-1β水平,加重心肌损伤,给予H2S抑制剂可以减轻心肌损伤.     

C5aR和P38-MAPK在脓毒性休克大鼠心肌损伤中的作用

Objective To investigate effects of complement C5a receptor and P38-MAPK on myocardial injury brought about by septic shock in rats. Method The early septic shock models were established by the method of cecal ligature and incision (CLI). A total of 30 Sprague-Dawley rats were randomly( random number) divided into normal control group ( n = 6 ) and model group ( n = 24 ) and the model group was further 12 hours later divided into 12 h subgroup (n = 12) and 24 h subgroup (n = 12). The arterial blood samples were collected 12 hours later for detecting the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and then the rats were sacrificed and the myocardial tissues were taken to assay the expressions of C5a receptor and P38-MAPK by using immunohistochemistry after HE staining. And the above procedure as did in 12 h subgroup was done 24 hours later. Results Compared with the control group, the levels of LDH and CK in rats of Model group were significantly higher (P ＜ 0. 05). There were significant differences in LDH and CK between 24 h subgroup and 12 h subgroup [(2 568.9 ± 280) vs. (2 201.2 ± 149)] and [(5 029.7±458) vs. (2 629.4±140)] ,P＜0. 05, P＜0.05. The analysis of C5aR and P38-MAPK gray values showed that there were significant differences between the model group and normal control group [(702.77 ±122) vs. (388.36±113)], P＜0. 05 and [(646.40±181) vs. (307.32 ±61)] ,P＜0.05,and those differences also found between the 24 h subgroup and 12 h subgroup. There was a significant positive correlation between C5aR and P38-MAPK (P＜0.05 ), and also the P38-MAPK had significant positive relationships with LDH(P＜0.05) and CK (P＜0.05). Conclusions The C5aR strongly potentiates the P38-MAPK to induce myocardial injury by septic shock.     

Inhibition of C5AR1 impairs osteoclast mobilization and prevents bone loss

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Role of C5a-C5aR interaction in sepsis

C5a-C5aR signaling plays an essential role in innate immunity of neutrophils. However, excessive interaction of C5a-C5aR results in harmful effects in these cells. In sepsis, robust generation of C5a occurs; blockade of either C5a or C5aR greatly improves survival in experimental sepsis following cecal ligation and puncture (CLP). The beneficial effects derived from C5a-C5aR interaction are associated with preservation of neutrophil innate immune functions (chemotaxis, phagocytosis, respiratory burst), attenuation of the inflammatory reaction, amelioration of coagulopathy, alteration in adhesion molecule expression, and modulation of apoptosis. Following CLP, C5aR expression is significantly elevated in organs, perhaps setting the stage for C5a-induced organ dysfunction. In contrast, C5aR content on neutrophils drops significantly at early stages of sepsis and progressively increases at later time points. Re-expression of C5aR on neutrophils during sepsis appears to be associated with the functional recovery of neutrophil innate immune functions. Following CLP, there is a positive correlation between C5aR content on blood neutrophils and survival of individual animals; high levels of C5aR on neutrophils are associated with survival, whereas low levels of C5aR on neutrophils predict mortality. These data suggest that in sepsis C5a-C5aR signaling is excessive, resulting in paralysis of neutrophil function. Interception of either C5a or C5aR dramatically improves survival during experimental sepsis.     

C5aR和P38-MAPK在脓毒性休克大鼠心肌损伤中的作用

目的 研究补体C5a受体与P38-MAPK在脓毒性休克情况下诱导心肌损伤的关系.方法 采用盲肠结扎剪切法构建早期脓毒性休克大鼠动物模型,实验地点在武汉大学人民医院麻醉科实验室.30只Sprague-Dawley大鼠随机(随机数字法)分为正常对照组6只和模型组24只(12 h组12只,24 h组12只).12 h组于术后12 h时点检测血清乳酸脱氢酶(LDH)和肌酸激酶(CK)水平,12 h后麻醉处死大鼠,迅速开胸取出心脏组织,行HE染色、应用免疫组织化学方法检测C5a受体和P38-MAPK的表达情况.24 h组亦于术后24 h时点检测血清LDH和CK值,24 h后处死大鼠取心肌组织行HE染色、检测C5a受体和P38-MAPK的表达情况.结果 模型组(12 h组和24 h组)与正常对照组相比,LDH值和CK值均明显升高(P＜0.05).24 h组LDH值和CK值与12 h时间点相比,差异具有统计学意义[(2 568.9±280)vs.(2 201.2±149),(5 029.7±458)vs.(2 629.4±140),P＜0.05].C5aR和P38-MAPK灰度值分析显示,模型组与正常对照组相比,均有显著性增高(P＜0.05),24 h组较12 h组相比,差异具有统计学意义[(702.77±122)vs.(388.36±113),(646.40±181)vs.(307.32±61),P＜0.05].相关分析显示C5aR和P38-MAPK存在显著正相关关系,(P＜0.05),P38-MAPK与LDH和CK均存在显著正相关关系(P＜0.05).结论 C5a受体和P38-MAPK在诱导脓毒性休克心肌损伤中有着强大的协同效应.

Abstract：

Objective To investigate effects of complement C5a receptor and P38-MAPK on myocardial injury brought about by septic shock in rats. Method The early septic shock models were established by the method of cecal ligature and incision (CLI). A total of 30 Sprague-Dawley rats were randomly( random number) divided into normal control group ( n = 6 ) and model group ( n = 24 ) and the model group was further 12 hours later divided into 12 h subgroup (n = 12) and 24 h subgroup (n = 12). The arterial blood samples were collected 12 hours later for detecting the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and then the rats were sacrificed and the myocardial tissues were taken to assay the expressions of C5a receptor and P38-MAPK by using immunohistochemistry after HE staining. And the above procedure as did in 12 h subgroup was done 24 hours later. Results Compared with the control group, the levels of LDH and CK in rats of Model group were significantly higher (P ＜ 0. 05). There were significant differences in LDH and CK between 24 h subgroup and 12 h subgroup [(2 568.9 ± 280) vs. (2 201.2 ± 149)] and [(5 029.7±458) vs. (2 629.4±140)] ,P＜0. 05, P＜0.05. The analysis of C5aR and P38-MAPK gray values showed that there were significant differences between the model group and normal control group [(702.77 ±122) vs. (388.36±113)], P＜0. 05 and [(646.40±181) vs. (307.32 ±61)] ,P＜0.05,and those differences also found between the 24 h subgroup and 12 h subgroup. There was a significant positive correlation between C5aR and P38-MAPK (P＜0.05 ), and also the P38-MAPK had significant positive relationships with LDH(P＜0.05) and CK (P＜0.05). Conclusions The C5aR strongly potentiates the P38-MAPK to induce myocardial injury by septic shock.     

C5a对内皮细胞表达血栓调节蛋白的影响

目的 探讨补体C5a对人脐静脉内皮细胞(HUVECs)血栓调节蛋白(TM)表达的影响.方法 体外培养HUVECs,以终浓度200 μg/L重组人C5a刺激HUVECs 8、12、16、20 h以及以终浓度100、200、300 μg/L的C5a刺激HUVECs 12 h,采用实时荧光定量聚合酶链反应(PCR)、蛋白质免疫印迹法(Western blotting)分别检测TM的mRNA及蛋白表达变化;观察C5a对其表达TM的时-效和量-效关系.结果 C5a抑制了HUVECs在TM的mRNA和细胞膜表面蛋白水平表达.同时,C5a对TM表达的抑制作用存在时-效关系[8、12、16、20 h时蛋白为(93.11±1.57)×10-2、(71.05±3.39)×10-2、(65.48±4.28)×10-2、(62.69±4.03)×10-2,mRNA为(301.71±80.40)×10-6、(38.29±20.24)×10-6、(8.82±2.66)×10-6、(7.05±0.80)×10-6],且均于12 h后降低程度明显减缓(P均<0.05);并存在量-效关系[C5a 100、200、300 mg/L时蛋白为(113.25±3.97)×10-2、(80.18±2.56)×10-2、(73.22±4.36)×10-2,mRNA为(401.77±20.46)×10-6、(31.12±3.51)×10-6、(18.19±1.46)×10-6],TM蛋白在C5a 300 μg/L、mRNA在C5a 200 μg/L时刺激12 h降低程度明显减缓(P均<0.05).结论 C5a通过抑制TM的结构基因表达,进而减弱TM的蛋白翻译,从而参与了脓毒症时凝血亢进、炎症损害的病理生理过程.     

High C5a levels are associated with increased mortality in sepsis patients--no enhancing effect by actin-free Gc-globulin

Background

Immune paralysis of phagocytic cells due to excess of the complement activation product C5a has been proposed as a critical pathomechanism in sepsis. In vitro studies suggest an interaction of C5a with Group-specific globulin (Gc-globulin).

Study objectives

To examine the predictive value of serum concentrations of both, C5a and actin-free Gc-globulin, and their ratio for prognosis (mortality) of critically ill patients.

Patients

154 critically ill (septic and non-septic) adult patients admitted to a Medical ICU and 38 healthy controls.

Measurements

Actin-free Gc-globulin and C5a were measured on ICU admission, alongside extensive laboratory, clinical and prospective outcome measures.

Results

Actin-free Gc-globulin and C5a serum concentrations were significantly reduced in critically ill patients compared with healthy controls. C5a levels, but not actin-free Gc-globulin, were significantly lower in patients with sepsis (n = 112) than in critically ill patients without sepsis (n = 42). C5a serum level was a prognostic parameter in patients with sepsis: High C5a levels were associated with increased mortality (at ICU and during follow-up). Although C5a and actin-free Gc-globulin were positively correlated, increasing serum concentrations of actin-free Gc-globulin did not enhance the C5a dependent effects in terms of prognosis or mortality in septic patients.

Conclusions

Investigation for C5a and/or actin-free Gc-globulin serum levels upon admission to the ICU may be helpful diagnostic tools. In patients with sepsis, C5a levels are an independent predictor of prognosis. However, different to pre-existing in vitro data, a clinically relevant interaction between actin-free Gc-globulin and C5a in terms of prognosis in severe inflammatory conditions is not given.     

人重组C5a对微血管内皮细胞表达组织因子的影响

目的 研究人重组C5a (human-recombinant C5a,rh-C5a)对人肺微血管内皮细胞(human pulmonary microvascular endothelial cells, HPMECs)表达组织因子(tissue factor,TF)的影响.方法 用不同浓度(100、200、300 μg/L)的rh-C5a刺激HPMECs 8 h和同一浓度(200 μg/L)的rh-C5a刺激HPMECs 4、8、12 h.采用实时荧光定量PCR和Western blot方法检测TF基因和蛋白表达情况.选取刺激浓度为200 μg/L,作用时间为8 h组进行C5a反义肽R4干预,相同的方法检测TF基因和蛋白表达并用免疫组织化学方法定性检测NF-κB p65变化. 结果正常的HPMECs基本不表达TF,rh-C5a刺激后,TF mRNA和蛋白开始表达,刺激的12 h内呈现出时效和量效关系(P<0.05).用C5a反义肽R4干预后,TF mRNA水平降至未干预组的68%(P<0.05),蛋白表达也有下降.免疫组织化学示p65在胞浆内明显增加并有部分入核.结论 在刺激的12 h内,C5a对HPMECs表达TF 存在时间-浓度的依赖关系,机制可能是C5a与其受体结合后,通过细胞信号转导途径活化NF-κB,从而调节基因和蛋白的表达.     

血浆补体C5a预示创伤失血性休克大鼠肝脏损害严重性

目的 探讨血浆补体C5a和C5b-9是否能够预示大鼠创伤失血性休克时肝脏损害的严重程度.方法 50只雄性健康Wistar大鼠被随机(随机数字法)分为正常组、模型1,3,6,24 h组.用酶联免疫吸附方法(ELISA)检测血浆中总补体活性CH50、补体活性片断C5a和膜攻击复合物C5b9,速率法检测血浆中谷草转氨酶.石蜡切片观察肝脏病理损害.结果 在模型1 h时,CH50显著上升并且达到最高值,3 h开始下降,24 h时达到最低点,1 h与3,6,24 h时点相比较,差异具有统计学意义(P<0.05);在正常组血中可以检测到少量的C5b-9,在模型1 h时C5b-9显著上升达到峰值,与正常组、模型3,6,24 h相比较差异均具有统计学意义(P<0.05),3 h时C5b-9开始下降,模型24 h时降至最低;模型组3,6,24 h时点血浆中C5a开始上升,与正常组相比较,差异均具有统计学意义(P<0.05),模型24 h组达到峰值;谷草转氨酶在模型1 h显著上升,在24 h达到峰值,24 h组与其余模型组及正常组相比较差异具有统计学意义(P<0.05).结论 创伤失m性休克时存在补体的大量活化,早期CH50、C5b-9上升;后期C5a上升.可以认为C5b-9是肝脏损害的启动因素.早期低水平的C5a可能是机体的一种自我保护措施,后期高水平的C5a作为自身不能代偿后的一种表现,作为后期疾病严重程度的一项预测指标.

Abstract：

Objective To discuss the feasibility of using serum complement C5a and C5b-9 as predictive indicators of liver injury severity in traumatic rats with hemorrhagic shock.Method Fifry healthy male Wistar rats were randomly(random number)divided into normal group,model 1 hour group,model 3 hours group,model 6 hours group,and model 24 hours group.Plasma CH50,C5a and C5b-9 were detected by using enzyme-linked immunosorbent assay,and rate method was used for determination of plasma aspartate aminotransferase.Paraffin sections of hepatic tissues were used to observe the damage of liver.Results In the model l h group,the CH50 increased significantly and reached the highest value,it began to decline in 3 hours group,and it reached the lowest point in 24 hours group.Compared with the model 3 hours group,6 hours group,and 24 hours group,the level of CH50 in model 1 hour group increased more significantly(respectively P<0.05).A small amount of C5b-9 in the normal group was detected.In the model 1 h group,C5b-9 increased significantly and reach the peak compared with 3hours group,6hours group and 24 hours group,respectively(P<0.05),but in the model 3hours,it began to decline,and in 24 hours group,it reduced to minimum.C5a increased insignificantly in the model 3 hours group,6 hours group and 24 hours group,and peaked in 24 hours group compared with normal group(P<0.05).Aspartate aminotransferase in the model 1 hour group increased significantly and peaked in 24 hours group compared with other groups(P<0.05).Conclusions A large number of complements are activated in the seRing of hemorrhagie shock.C5b-9 and CH50 increase significantly in the early stage,and C5a.increases significantly in the later stage.C5b-9 can be considered as,an initiative factor of liver injury.The low levels of C5a in the early stage may be a mechanism of self-protection of the body.The high levels of CSa in the later stage may be a kind of decompensation,and C5a can be used as a late predictor of disease severity.     

PPP2R5C基因结构特点和生物学功能

PPP2RSC是蛋白磷酸酶2A的调节性亚单位中一个家族成员，它在调节细胞增殖、分化和转化等方面具有重要作用，其作用主要通过对P53蛋白某些位点氨基酸的去磷酸化而实现。近期研究提示，PPP2R5C基因表达模式的改变与细胞恶性转化相关；此外，有研究发现PPP2R5C可以作为B—CLL病情进展的相关标记。本文就PPP2R5C基因结构、生物学功能及PPP2R5C基因与肿瘤发生发展的关系进行了探讨。