目的 觀察雙歧桿菌三聯(lián)活菌膠囊聯(lián)合烏司他丁對膿毒癥機(jī)械通氣患者腸道菌群及外周血核苷酸結(jié)合寡聚化結(jié)構(gòu)域樣受體3（NLRP3）、半胱氨酸天冬氨酸酶-1（Caspase-1）的影響。方法 回顧性收集2017年1月—2020年12月重慶市急救醫(yī)療中心收治的98例膿毒癥機(jī)械通氣患者為研究對象，按照治療方法不同分為對照組和試驗(yàn)組，每組各49例。所有患者均予以常規(guī)基礎(chǔ)治療，對照組采用烏司他丁注射液治療，每次靜脈滴注1.0×10⁵ U，每天3次；試驗(yàn)組在對照組基礎(chǔ)上加用雙歧桿菌三聯(lián)活菌膠囊治療，口服，每次0.42 g，每天2次。兩組均在治療7 d后評估治療效果。比較兩組療效、機(jī)械通氣時(shí)間、癥狀改善時(shí)間、ICU入住時(shí)間、住院時(shí)間，分別于治療前、治療7 d后檢測腸道菌群（雙歧桿菌、乳酸桿菌、葡萄球菌）菌含量、黏膜屏障功能指標(biāo)［二胺氧化酶（DAO）、D-乳酸、內(nèi)毒素（ET）］、免疫功能相關(guān)指標(biāo)（CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺）水平及外周血NLRP3、Caspase-1蛋白水平，觀察兩組治療期間的不良反應(yīng)發(fā)生情況。結(jié)果 試驗(yàn)組總有效率為91.84%，較對照組的75.51%顯著升高（P＜0.05）。試驗(yàn)組患者機(jī)械通氣時(shí)間、癥狀改善時(shí)間、ICU入住時(shí)間、住院時(shí)間均顯著短于對照組（P＜0.05）。治療前兩組患者腸道雙歧桿菌、乳酸桿菌、葡萄球菌含量比較，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療7 d后兩組患者腸道雙歧桿菌和乳酸桿菌含量均顯著升高（P＜0.05），葡萄球菌含量較治療前顯著降低（P＜0.05）；治療7 d后試驗(yàn)組患者腸道雙歧桿菌、乳酸桿菌含量顯著高于對照組，葡萄球菌含量顯著低于對照組（P＜0.05）。治療前兩組患者血清DAO、D-乳酸、ET水平比較，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療7 d后兩組患者血清DAO、D-乳酸、ET水平均較治療前顯著降低（P＜0.05），試驗(yàn)組治療后血清DAO、D-乳酸、ET水平均顯著低于對照組（P＜0.05）。治療前兩組患者外周血CD3＋、CD4+、CD8+、CD4+/CD8+水平比較，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療7 d后兩組外周血CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平均較治療前顯著升高（P＜0.05），CD8+水平較治療前顯著降低（P＜0.05）；治療后試驗(yàn)組外周血CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平均顯著高于對照組（P＜0.05），CD8⁺顯著低于對照組（P＜0.05）。治療前兩組外周血NLRP3、Caspase-1蛋白水平比較，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）；治療7 d后兩組外周血NLRP3、Caspase-1蛋白水平均較治療前顯著降低（P＜0.05），治療后試驗(yàn)組外周血NLRP3、Caspase-1蛋白水平均顯著低于對照組（P＜0.05）。兩組不良反應(yīng)總發(fā)生率比較，差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）。結(jié)論 雙歧桿菌三聯(lián)活菌膠囊聯(lián)合烏司他丁治療膿毒癥機(jī)械通氣患者效果顯著，可有效縮短患者機(jī)械通氣時(shí)間、癥狀改善時(shí)間、ICU入住時(shí)間、住院時(shí)間，恢復(fù)腸道菌群平衡，提高黏膜屏障功能及免疫功能，調(diào)節(jié)外周血NLRP3、Caspase-1水平，且安全性高。

Objective To explore the effect of Bifidobacterium Triple Viable Capsules combined with ulinastatin on intestinal flora and peripheral blood nucleotide binding oligomerization domain-like receptor 3 (NLRP3), Caspase-1 (Caspase-1) of sepsis patients with mechanical ventilation. Methods A total of 98 patients with sepsis treated by mechanical ventilation in Chongqing Emergency Medical Center from January 2017 to December 2020 were collected retrospectively. They were divided into control group and experimental group according to different treatment methods, with 49 cases in each group. All patients were given routine basic treatment, and patients in the control group were treated with Ulinastatin Injection, with 1.0×10⁵ U intravenous drip each time, three times a day. On the basis of the control group, patients in the experimental group were treated with Bifidobacterium Triple Viable Capsule, orally, 0.42 g each time, twice a day. Both groups were evaluated after seven days of treatment. The curative effect, mechanical ventilation time, symptom improvement time, ICU stay time and hospitalization time of two groups were compared. The bacterial content of intestinal flora (Bifidobacterium, Lactobacillus and Staphylococcus), mucosal barrier function indexes [diamine oxidase (DAO), D-lactic acid, endotoxin (ET)], immune function related indexes (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺) and peripheral blood NLRP3 and Caspase-1 protein levels were measured before and seven days after treatment. The adverse reactions of the two groups during treatment were observed. Results The total effective rate in the experimental group was 91.84%, which was significantly higher than 75.51% in the control group (P<0.05). The duration of mechanical ventilation, symptom improvement, ICU stay and hospital stay in the experimental group were significantly shorter than those in the control group (P<0.05). There was no significant difference in the contents of intestinal Bifidobacteria, Lactobacillus and Staphylococcus between the two groups before treatment (P>0.05). After seven days of treatment, the contents of intestinal Bifidobacteria and Lactobacillus in the two groups increased significantly (P<0.05), and the content of Staphylococcus decreased significantly (P<0.05). After seven days of treatment, the contents of Bifidobacterium and Lactobacillus in the experimental group were significantly higher than those in the control group, and the contents of Staphylococcus were significantly lower than those in the control group (P<0.05). There was no significant difference in the levels of serum DAO, D-lactic acid and ET between two groups before treatment (P>0.05). After seven days of treatment, the levels of serum DAO, D-lactic acid and ET in the two groups were significantly lower than those before treatment (P<0.05). The levels of serum DAO, D-lactic acid and ET in the experimental group were significantly lower than those in the control group (P<0.05). Before treatment, there was no significant difference in the levels of CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺in peripheral blood of patients in two groups (P>0.05). After seven days of treatment, the levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺ in peripheral blood of the two groups were significantly higher than those before treatment (P<0.05), and the level of CD8+ was significantly lower than that before treatment (P<0.05). After treatment, the levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺ in peripheral blood of the experimental group were significantly higher than those in the control group (P<0.05), and CD8⁺ was significantly lower than those in the control group (P<0.05). There was no significant difference in peripheral blood NLRP3 and Caspase-1 protein levels between the two groups before treatment (P>0.05). After seven days of treatment, the levels of peripheral blood NLRP3 and Caspase-1 protein in two groups were significantly lower than those before treatment (P<0.05). After treatment, the levels of peripheral blood NLRP3 and Caspase-1 protein in the experimental group were significantly lower than those in the control group (P<0.05). There was no significant difference in the total incidence of adverse reactions between two groups (P>0.05). Conclusion Bifidobacterium Triple Viable Capsule combined with ulinastatin is effective in treatment of septic patients with mechanical ventilation. It can effectively shorten the time of mechanical ventilation, symptom improvement, ICU stay and hospital stay, restore the balance of intestinal flora, improve the function of mucosal barrier and immunity, regulate the levels of peripheral blood NLRP3 and Caspase-1, and has high safety.

R977.3