Suzuki Takeshi, Inoue Kei, Igarashi Toru, Kato Jungo, Nagata Hiromasa, Yamada Takashige, Minamishima Shizuka, Morisaki Hiroshi
Tokai University School of Medicine, Department of Anesthesiology, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Keio University School of Medicine, Department of Anesthesiology, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Crit Care Res Pract. 2019 Dec 11;2019:8157482. doi: 10.1155/2019/8157482. eCollection 2019.
Lymphocyte cell death contributes to sepsis-induced immunosuppression, leading to poor prognosis. This study examined whether sepsis severity and beta-blocker therapy could affect the degree of T-lymphocyte cell death in a mouse model of sepsis. In the first control study, 20 animals were allocated to 4 groups: control group with sham operation (group C, = 5) and 3 groups with cecum ligation and puncture (CLP) performed at 3 different sites: proximal, middle, and distal cecum (groups CLP-P, CLP-M, and CLP-D, respectively; = 5 in each group). Their spleens were resected under general anesthesia 24 hours after CLP, and the total number of normal splenic T lymphocytes per mouse and the percentage of apoptotic T lymphocytes were evaluated using flow cytometry. In the second experimental study, the effect of the beta-blocker esmolol was examined in CLP-P (group CLP-PE vs. CLP-P; = 5 in each group). The total normal splenic T-lymphocyte numbers per mouse significantly decreased in proportion to CLP severity (group C, 18.6 × 10 (15 × 10-23.6 × 10); CLP-D, 9.2 × 10 (8.8 × 10-9.8 × 10); CLP-M, 6.7 × 10 (6.3 × 10-7.0 × 10); and CLP-P, 5.3 × 10 (5.1 × 10-6.8 × 10)). Beta-blocker therapy restored T-lymphocyte numbers (group CLP-PE vs. CLP-P; 6.94 ± 1.52 × 10 vs. 4.18 ± 1.71 × 10; =0.027) without affecting apoptosis percentage. Beta-blocker therapy might improve sepsis-induced immunosuppression via normal splenic T-lymphocyte preservation.
淋巴细胞死亡会导致脓毒症诱导的免疫抑制,进而导致预后不良。本研究探讨了脓毒症严重程度和β受体阻滞剂治疗是否会影响脓毒症小鼠模型中T淋巴细胞死亡程度。在第一项对照研究中,将20只动物分为4组:假手术对照组(C组,n = 5)和3组在盲肠3个不同部位进行盲肠结扎和穿刺(CLP)的组,分别为近端、中部和远端盲肠(分别为CLP-P组、CLP-M组和CLP-D组;每组n = 5)。在CLP术后24小时,在全身麻醉下切除它们的脾脏,使用流式细胞术评估每只小鼠脾脏中正常T淋巴细胞的总数以及凋亡T淋巴细胞的百分比。在第二项实验研究中,在CLP-P组中研究了β受体阻滞剂艾司洛尔的作用(CLP-PE组与CLP-P组比较;每组n = 5)。每只小鼠脾脏中正常T淋巴细胞的总数与CLP严重程度成比例显著下降(C组,18.6×10(15×10 - 23.6×10);CLP-D组,9.2×10(8.8×10 - 9.8×10);CLP-M组,6.7×10(6.3×10 - 7.0×10);CLP-P组,5.3×10(5.1×10 - 6.8×10))。β受体阻滞剂治疗可恢复T淋巴细胞数量(CLP-PE组与CLP-P组比较;6.94±1.52×10对4.18±1.71×10;P = 0.027),且不影响凋亡百分比。β受体阻滞剂治疗可能通过保留正常脾脏T淋巴细胞来改善脓毒症诱导的免疫抑制。