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[肌肉幼虫排泄分泌蛋白对脓毒症小鼠心肌损伤的保护作用]

[Protective effect of excretory-secretory proteins from muscle larvae against myocardial injury in septic mice].

作者信息

Yuan Y, Nian F, Li H, Yang H, Wu Y, Ma M, Wang K, Chen X, Zhang Z, Li G, Yang X, Wu Q

机构信息

Department of Human Anatomy, Bengbu Medical College, Bengbu 233000, China.

Department of Oncology, Bengbu Third People's Hospital Affiliated to Bengbu Medical College, Bengbu 233000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jun 20;42(6):824-831. doi: 10.12122/j.issn.1673-4254.2022.06.05.

Abstract

OBJECTIVE

To evaluate the protective effect of excretory-secretory proteins from muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.

METHODS

Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.

RESULTS

Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h ( < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI ( < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate ( < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI ( < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF- and IL-6 levels in the serum and myocardial tissue ( < 0.001), which were significantly lowered by treatment with TS-MES ( < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice ( < 0.05).

CONCLUSION

Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.

摘要

目的

评估旋毛虫肌幼虫排泄分泌蛋白(Ts-MES)对脓毒症诱导的小鼠心肌损伤的保护作用。

方法

80只雄性BALB/C小鼠随机等分为假手术组、心肌损伤组、Ts-MES治疗组和地塞米松治疗组。后3组通过盲肠结扎穿孔建立脓毒症诱导的心肌损伤模型;假手术仅暴露盲肠,不进行结扎或穿孔。术后40分钟,按要求给小鼠腹腔注射150 μL PBS、20 μg Ts-MES或0.3 mg/kg地塞米松。术后12小时,每组随机选取6只小鼠进行超声心动图检查,8只小鼠用于观察72小时内的生存率。其余6只小鼠进行HE染色观察心肌病理变化,用ELISA检测血清NTPro-BNP和cTnI水平;用ELISA和qRT-PCR检测血清及心肌组织中TNF-、IL-6、IL-10和TGF-β的表达。

结果

与假手术小鼠相比,脓毒症小鼠的心功能指标(LVEF、LVFS和E/A)显著降低,72小时内生存率降低(<0.001),心肌损伤评分及血清NTPro-BNP和cTnI水平显著升高(<0.01)。Ts-MES治疗显著改善了脓毒症小鼠的心功能和72小时生存率(<0.05),降低了心肌损伤评分及血清NTPro-BNP和cTnI水平(<0.05)。与假手术小鼠相比,脓毒症小鼠血清和心肌组织中TNF-和IL-6水平明显升高(<0.001),Ts-MES治疗显著降低了这些水平(<0.05)。Ts-MES和地塞米松均提高了脓毒症小鼠IL-10和TGF-β水平,但仅Ts-MES治疗组变化显著(<0.05)。

结论

Ts-MES可通过减少促炎细胞因子的产生和提高调节性细胞因子水平来保护脓毒症小鼠免受心肌损伤。

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