脓毒症中的免疫“失和谐”现象(英文)

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脓毒症是由于病原体侵入体内,由其毒素引致对组织器官有害的剧烈炎症的一组综合症状。它并不能称为疾病,但由于其发病机制至今仍未被透彻地阐明,其发病率和病死率仍然很高。对脓毒症的研究已进行得很广泛和深入,很多学者已注意到在其发病机制中免疫功能的混乱殊为重要,其中尤为突出的是免疫功能的“不和谐”现象,既存在剧烈的炎症反应,同时又出现免疫抑制。当机体受到猛烈袭击时,大量的补体通过旁路途径裂解而产生过敏毒素C5a。后者抑制中性白细胞的杀菌功能,因而突增患者易感性。病原体在感染后释放出的毒素却抑制了中性白细胞的凋亡,其结果是大量已浸润入感染组织的中性白细胞不能凋亡和脱颗粒,释放大量的蛋白酶和氧自由基,使炎症反应加剧和持久。同时由于晚期促炎介质高迁移率族蛋白B-1 (HMGB-1)的介入,更使炎症加剧。其时皮肤内的大量的树突状细胞由于广泛深度烧伤而被毁,脾脏内的树突状细胞也因炎症反应而丢失,抗原呈递功能极度降低。更由于体内淋巴细胞发生大范围的凋亡,因此天然免疫功能显著抑制。一方面是剧烈的炎症反应,另一方而是免疫功能抑制,形成免疫不协调或“不和谐”。根据这些现象进行应用乌司他丁和α-1胸腺肽进行多中心临床试验治疗,由于前者具有抑制炎症及蛋白酶的功能,而α-1胸腺肽提升抗原呈递功能和抑制胱天蛋白酶-3(Caspase-3),因此获得可喜的治疗结果,死亡率显著降低,APACHEⅡ和Marshall评分降低。良好的治疗证明了上述的观点是可信的。 Sepsis is a group of syndromes of violent inflammation caused by pathogens invade the body and causing their toxins to be harmful to tissues and organs. It can not be called a disease, but its morbidity and mortality are still high, as its pathogenesis has not been thoroughly elucidated so far. Researches on sepsis have been carried out extensively and deeply. Many scholars have noticed that it is very important for the disorder of immune function in its pathogenesis, among which the phenomenon of “disharmony” of immune function is especially prominent Severe inflammatory reaction, while immunosuppression. When the body is violently attacked, a large amount of complement is cleaved by the bypass pathway to produce anaphylatoxin C5a. The latter inhibits the neutrophil’s bactericidal function, thus suddenly increasing the patient’s susceptibility. The toxin released by the pathogen after infection inhibits the neutrophil apoptosis. As a result, a large number of neutrophils infiltrated into the infected tissue can not apoptosis and degranulate and release a large amount of proteases and oxygen free radicals, thereby causing inflammation Exacerbated and lasting. At the same time due to the late pro-inflammatory mediators high mobility group protein B-1 (HMGB-1) intervention, but also make the inflammation worse. In the meantime, a large number of dendritic cells in the skin are destroyed due to extensive and deep burns. Dendritic cells in the spleen are also lost due to an inflammatory reaction and the antigen presenting function is extremely reduced. More due to a wide range of body lymphocytes apoptosis, so the natural immune function was significantly inhibited. On the one hand is a violent inflammatory response, the other is immune suppression, the formation of immune incompatibility or “discordant.” According to these phenomena, ulinastatin and α-1 thymosin are used in multicenter clinical trials. Since the former has the function of inhibiting inflammation and protease, α-1 thymosin enhances antigen presenting function and inhibits caspase- 3), thus obtaining gratifying treatment outcomes with significantly reduced mortality and reduced APACHE II and Marshall scores. Good treatment proves the above point of view is credible.
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