双歧杆菌三联活菌胶囊联合乌司他丁对脓毒症机械通气患者肠道菌群及外周血NLRP3、Caspase-1的影响

目的 观察双歧杆菌三联活菌胶囊联合乌司他丁对脓毒症机械通气患者肠道菌群及外周血核苷酸结合寡聚化结构域样受体3（NLRP3）、半胱氨酸天冬氨酸酶-1（Caspase-1）的影响。方法 回顾性收集2017年1月—2020年12月重庆市急救医疗中心收治的98例脓毒症机械通气患者为研究对象，按照治疗方法不同分为对照组和试验组，每组各49例。所有患者均予以常规基础治疗，对照组采用乌司他丁注射液治疗，每次静脉滴注1.0×10⁵ U，每天3次；试验组在对照组基础上加用双歧杆菌三联活菌胶囊治疗，口服，每次0.42 g，每天2次。两组均在治疗7 d后评估治疗效果。比较两组疗效、机械通气时间、症状改善时间、ICU入住时间、住院时间，分别于治疗前、治疗7 d后检测肠道菌群（双歧杆菌、乳酸杆菌、葡萄球菌）菌含量、黏膜屏障功能指标［二胺氧化酶（DAO）、D-乳酸、内毒素（ET）］、免疫功能相关指标（CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺）水平及外周血NLRP3、Caspase-1蛋白水平，观察两组治疗期间的不良反应发生情况。结果 试验组总有效率为91.84%，较对照组的75.51%显著升高（P＜0.05）。试验组患者机械通气时间、症状改善时间、ICU入住时间、住院时间均显著短于对照组（P＜0.05）。治疗前两组患者肠道双歧杆菌、乳酸杆菌、葡萄球菌含量比较，差异无统计学意义（P＞0.05）；治疗7 d后两组患者肠道双歧杆菌和乳酸杆菌含量均显著升高（P＜0.05），葡萄球菌含量较治疗前显著降低（P＜0.05）；治疗7 d后试验组患者肠道双歧杆菌、乳酸杆菌含量显著高于对照组，葡萄球菌含量显著低于对照组（P＜0.05）。治疗前两组患者血清DAO、D-乳酸、ET水平比较，差异无统计学意义（P＞0.05）；治疗7 d后两组患者血清DAO、D-乳酸、ET水平均较治疗前显著降低（P＜0.05），试验组治疗后血清DAO、D-乳酸、ET水平均显著低于对照组（P＜0.05）。治疗前两组患者外周血CD3＋、CD4+、CD8+、CD4+/CD8+水平比较，差异无统计学意义（P＞0.05）；治疗7 d后两组外周血CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平均较治疗前显著升高（P＜0.05），CD8+水平较治疗前显著降低（P＜0.05）；治疗后试验组外周血CD3^＋、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平均显著高于对照组（P＜0.05），CD8⁺显著低于对照组（P＜0.05）。治疗前两组外周血NLRP3、Caspase-1蛋白水平比较，差异无统计学意义（P＞0.05）；治疗7 d后两组外周血NLRP3、Caspase-1蛋白水平均较治疗前显著降低（P＜0.05），治疗后试验组外周血NLRP3、Caspase-1蛋白水平均显著低于对照组（P＜0.05）。两组不良反应总发生率比较，差异无统计学意义（P＞0.05）。结论 双歧杆菌三联活菌胶囊联合乌司他丁治疗脓毒症机械通气患者效果显著，可有效缩短患者机械通气时间、症状改善时间、ICU入住时间、住院时间，恢复肠道菌群平衡，提高黏膜屏障功能及免疫功能，调节外周血NLRP3、Caspase-1水平，且安全性高。

Effects of Bifidobacterium Triple Viable Capsule combined with ulinastatin on intestinal flora and peripheral blood NLRP3 and Caspase-1 in patients with septic mechanical ventilation

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.