脓毒症大鼠通过降低肌浆网钙摄取和SERCA1表达损害膈肌舒张功能

发布时间：2018-01-06 08:05

本文关键词：脓毒症大鼠通过降低肌浆网钙摄取和SERCA1表达损害膈肌舒张功能　出处：《南方医科大学学报》2017年04期 　论文类型：期刊论文

【摘要】：目的探讨脓毒症急性期大鼠膈肌舒张功能障碍的机制。方法雄性清洁级SD大鼠36只。随机数字表法分为:假手术组(S组)12只、造模组(CLP组)24只。对造模组行盲肠结扎穿孔手术复制脓毒症模型,造模成功后随机分为脓毒症CLP-6 h组和脓毒症CLP-12 h组,各12只,分别于术后6 h和12 h测定单刺激肌颤搐(Pt)、最大强直收缩力(Po)、半舒张时间(1/2RT)、收缩时间(TPT)、最大收缩期上升速率(+d F/dt)和最大舒张期下降速率(-d F/dt);运用Fura-2法测定膈肌肌浆网钙最大摄取率和释放率,Western blotting法检测肌浆网SERCA1、SERCA2和Ry R表达。结果造模后6 h和12 h组大鼠较S组半舒张时间显著延长,-d F/dt显著下降(P0.01),而仅仅在12 h组大鼠膈肌+d F/dt、Pt、Po和肌浆网钙的峰值释放率较S组显著降低(P0.01),6 h组大鼠未见明显变化(P0.05);造模后12 h组大鼠膈肌SERCA1和Ry R表达显著下降(P0.01),SERCA2和Ca~(2+)-ATP酶活性无明显改变(P0.05)。结论脓毒症大鼠急性期12 h内膈肌收缩和舒张功能显著受损,舒张功能障碍可能与肌浆网钙摄取功能下降及SERCA1低表达有关,肌浆网释放和摄取功能及Ry R表达下降共同导致了收缩功能的下降。
[Abstract]:Objective to investigate the mechanism of diaphragm diastolic dysfunction in acute sepsis rats. Methods Thirty-six male SD rats of clean grade were randomly divided into sham operation group (S group) and control group (n = 12). The sepsis model was established by cecal ligation and perforation in 24 rats in the model group. The model group was randomly divided into septic CLP-6 h group and septic CLP-12 h group. Each 12 rats were measured at 6 h and 12 h postoperatively for single stimulatory muscle twitch, maximal contractility, half diastolic time (1 / 2 RTT) and contraction time (TPTT). Maximum systolic rise rate (d F / DT) and maximal diastolic decline rate (D F / DT); The maximal calcium uptake rate and release rate of sarcoplasmic reticulum were measured by Fura-2 method. Western blotting method was used to detect sarcoplasmic reticulum SERCA1. Results the semidiastolic time of rats in the 6 h and 12 h groups was significantly longer than that in group S (P 0.01). However, the peak release rate of dF- dtttio and sarcoplasmic reticulum calcium in the diaphragm of rats in 12 h group was significantly lower than that in group S (P 0.01). In 6 h group, there was no significant change in P0.05; The expression of SERCA1 and Ry R in diaphragm of rats in 12 h group decreased significantly (P0.01). The activities of SERCA2 and Ca~(2 were not changed significantly (P 0.05). Conclusion the contractile and diastolic functions of the diaphragm in sepsis rats were significantly impaired within 12 hours during the acute phase of sepsis. Diastolic dysfunction may be related to the decrease of sarcoplasmic reticulum calcium uptake function and the low expression of SERCA1. The decrease of sarcoplasmic reticulum release and uptake function and the decrease of Ry R expression may lead to the decrease of systolic function.
【作者单位】：南京医科大学;上海交通大学附属第一人民医院麻醉科;
【基金】：国家自然科学基金(81171845) 上海自然科学基金(14ZR1438100)~~
【分类号】：R459.7
【正文快照】： 脓毒症是一种全身性的炎性综合症,可导致包括呼吸功能损伤在内的多器官功能障碍。脓毒症膈肌损伤会加重呼吸功能障碍,延长机械通气时间[1-2]。然而,脓毒症引起膈肌功能障碍的机制仍不十分明确。脓毒症不仅会引起的线粒体氧化应激损伤和能量代谢异常,同时会导致胞内钙稳态失衡[

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