Research of respiratory muscle failure : effects of cytokines IL-8, IL-10 and IL-13 on diaphragm muscle

呼吸肌衰竭研究：细胞因子IL-8、IL-10和IL-13对膈肌的影响

• 批准号: 12670545
• 负责人: SHINDOH Chiyohiko
• 金额: $ 2.18万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670545/
• 关键词: Muscle fatigue; ATPase staining; Respiratory muscle failure; サイトカイン

(1) Experimental setup : We have made an experimental setup for measurements of diaphragm muscle contractility with an organ bath and a PCR cycler, which we requested for an equipment. Using the experimental setup, we performed an experiment about what effects of cytokines of IL-8, IL-10 and IL-13 on diaphragm muscle.(2) Effects of IL-8 on diaphragm muscle : After IL-8 (3 μg/kg) was given via tail vein of Wistar rats, we measured force-frequency curves and twitch contractions at 0, 2 and 4 hours. IL-8 decreased significantly the force-frequency curves at 2 and 4 hours, and NO production was observed in type I (slow-twitch) and IIa (oxygenative-fast-twitch) muscle fibers in time-dependently.(3) Effects of IL-10 and IL-13 on diaphragm muscle : Both IL-10 and IL-13 prevented the decrease of force-frequency curves by endotoxin (30 mg/kg) which was given into peritoneal cavity of animals. They also inhibited NO production performed by NADPH diaphorase staining in the diaphragm muscle fibers.(4) From these results, it is suggested that IL-8 (a cytokine related to inflammation) causes deterioration of diaphragm muscle function and NO production in diaphragm muscle fibers. However, there is a protective mechanism of IL-10 and IL-13 (Th2 cytokines) to scavenge NO, and prevented diaphragm muscle deterioration induced by endotoxin. The present study suggests that these Th2 cytokines has a possibility of clinical application for treatment of respiratory muscle failure due to septicemia.

(1)实验装置：根据我们所要求的装置，我们制作了一套用器官浴和聚合酶链式反应循环仪测量横隔肌收缩能力的实验装置。(2)IL-8对横隔肌的影响：大鼠尾静脉注射IL-8(3μg/kg)后，分别于0、2、4h测力-频曲线及痉挛收缩。IL-8在2、4h显著降低力频曲线，且呈时间依赖性地在I型(慢抽动)和IIa(氧合快抽动)肌纤维中不产生。(3)IL-10和IL-13对横隔肌的影响：IL-10和IL-13均可拮抗内毒素(30 mg/kg)内毒素引起的力频曲线下降。通过NADPH黄递酶染色，它们还抑制了横隔肌纤维中NO的产生。(4)这些结果表明，IL-8(一种与炎症有关的细胞因子)导致横隔肌功能恶化和横隔肌纤维中NO的产生。而IL-10和IL-13(Th2型细胞因子)清除NO，防止内毒素所致的横隔肌退化，具有保护作用。本研究提示这些Th2细胞因子有可能用于败血症所致呼吸肌衰竭的临床治疗。

项目成果

M. Zuguchi, C. Shindoh. K. Chida, H. Saito, Y. Takai: "Safety and Clinical Benefits Trans-subxiphoidal Left Ventricular Puncture"Catheter. Cardio. Interven.. 55・1. 58-65 (2002)

M. Zuguchi、C. Shindoh. K. Chida、H. Saito、Y. Takai：“经剑突左心室穿刺的安全性和临床益处”心脏介入。55・1。

O.Taguchi,Y.Shindoh,D.Katayose,C.Shindoh: "Effects of Different Breathing Patterns on Oxygen Consumption of Respiratory Muscles."Bull.Coll.Med.Sci.Tohoku Univ.. 10・1. 13-22 (2001)

O.Taguchi、Y.Shindoh、D.Katayose、C.Shindoh：“不同呼吸模式对呼吸肌耗氧量的影响”。Bull.Coll.Med.Sci.Tohoku Univ.. 10・1。 2001）

O. Taguchi, Y. Shindoh. D. Katayose. C. Shindoh: "Effects of Different Breathing Patterns on Oxygen Consumption of Respiratory Muscles"Bull. Coll. Med. Sci. Tohoku Univ.. 10・1. 13-22 (2001)

O.田口，Y. Shindoh。C. Shindoh：“不同呼吸模式对呼吸肌肉耗氧量的影响”，东北大学医学杂志，10・1。 ）

E.Nakahata, et al.: "Interleukin-12 prevents diaphragm muscle deterioration in a septic animal model"Comp.Biochem.Physiol. 130・4. 653-663 (2001)

E. Nakahata 等：“Interleukin-12 预防脓毒症动物模型中的膈肌退化”Comp.Biochem.Physiol. 130・4 (2001)。

O.Taguchi, et al.: "Effects of Different Breathing Patterns on Oxygen Consumption of Respiratory Muscles"Bull. Coll. Med. Sci. Tohoku Univ.. 10・1. 13-22 (2001)

O.Taguchi 等：“不同呼吸模式对呼吸肌耗氧量的影响”Bull.Tohoku Univ. 10・1。