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在脓毒症模型中,β受体阻滞剂疗法可维持正常的脾脏T淋巴细胞数量,该数量会随着脓毒症严重程度成比例减少。

Beta-Blocker Therapy Preserves Normal Splenic T-Lymphocyte Numbers Reduced in Proportion to Sepsis Severity in a Sepsis Model.

作者信息

Suzuki Takeshi, Inoue Kei, Igarashi Toru, Kato Jungo, Nagata Hiromasa, Yamada Takashige, Minamishima Shizuka, Morisaki Hiroshi

机构信息

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.

出版信息

Crit Care Res Pract. 2019 Dec 11;2019:8157482. doi: 10.1155/2019/8157482. eCollection 2019.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f104/6927051/e4ca5e0c221a/CCRP2019-8157482.001.jpg

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