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强迫运动诱导性肌病大鼠模型中的性别依赖性代谢和行为改变

Sex-dependent metabolic and behavioural alterations in a rat model of forced exertion-induced myopathy.

作者信息

Lubbe Crystal, Harvey Brian H, Viljoen Francois P, Meyer Leith, Wolmarans De Wet

机构信息

Division of Pharmacology, Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.

MRC Research Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

出版信息

BMC Vet Res. 2025 Mar 22;21(1):194. doi: 10.1186/s12917-025-04650-x.

DOI:10.1186/s12917-025-04650-x
PMID:40119337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11929309/
Abstract

BACKGROUND

Mass boma capture (MBC) of ungulates may trigger a metabolic condition known as capture myopathy (CM), resulting in myoglobinuria and hyperthermia (rhabdomyolysis). Its pathobiology is poorly understood, especially the role of contextual reminders; a preclinical model system could thus be useful. Sixty (60) adult Sprague Dawley rats (30 rats per sex), divided into three experimental series (n = 12-24), were exposed to MBC-like exertion, viz., forced treadmill running (FTR) at 75% of VO (30 m/min) with and without aversive noise (context) until physical exhaustion. Rectal and surface temperatures were measured before and after reaching exhaustion. Urine myoglobin, plasma lactate dehydrogenase (LDH), lactate, and creatine kinase (CK) were measured immediately and 15 days after MBC. Anxiety was assessed in the light-dark and social interaction tests.

RESULTS

Male and female MBC rats presented with significant hyperthermia, with females showing significantly increased urine myoglobin immediately after MBC, although this was not sustained until day 15 post MBC. LDH was significantly elevated in female rats at baseline but not day 15 post-MBC. Contextual re-exposure prior to testing on day 15 resulted in significant sex-dependent differences in myoglobin and CK concentrations, with female rats being significantly more affected. Only female rats trended towards increased anxiety-like behaviour immediately post-MBC exposure, which was not sustained until day 15 post MBC.

CONCLUSIONS

This work builds on previous research using a rodent model of capture myopathy (CM) that confirmed the running protocol to effectively elicite the necessary muscular response. The MBC protocol emphasizes hyperthermia and increased urine myoglobin, sensitivity to contextual reminder (noise), and a trend towards anxiety, particularly in females, highlighting sex-specific physiological responses. By incorporating behavioural and biochemical assessments, acute versus delayed response and environmental triggers, the study enhances model validity and deepens insights into CM-related responses.

摘要

背景

有蹄类动物的大规模群体捕获(MBC)可能引发一种称为捕获性肌病(CM)的代谢状况,导致肌红蛋白尿和体温过高(横纹肌溶解)。其病理生物学尚不清楚,尤其是情境提示的作用;因此,一个临床前模型系统可能会有所帮助。六十只成年Sprague Dawley大鼠(雌雄各30只),分为三个实验系列(n = 12 - 24),暴露于类似MBC的运动中,即,在有和没有厌恶噪音(情境)的情况下,以75%的最大摄氧量(30米/分钟)进行强迫跑步机跑步(FTR),直至体力耗尽。在达到疲惫前后测量直肠温度和体表温度。在MBC后立即和15天测量尿肌红蛋白、血浆乳酸脱氢酶(LDH)、乳酸和肌酸激酶(CK)。在明暗和社交互动测试中评估焦虑情况。

结果

雄性和雌性MBC大鼠均出现显著的体温过高,雌性大鼠在MBC后立即显示尿肌红蛋白显著增加,尽管在MBC后15天未持续。雌性大鼠在基线时LDH显著升高,但在MBC后15天未升高。在第15天测试前再次暴露于情境中,导致肌红蛋白和CK浓度出现显著的性别差异,雌性大鼠受影响更显著。仅雌性大鼠在MBC暴露后立即有焦虑样行为增加的趋势,但在MBC后15天未持续。

结论

这项工作建立在先前使用捕获性肌病(CM)啮齿动物模型的研究基础上,该研究证实了跑步方案能有效引发必要的肌肉反应。MBC方案强调体温过高和尿肌红蛋白增加、对情境提示(噪音)的敏感性以及焦虑趋势,尤其是在雌性中,突出了性别特异性生理反应。通过纳入行为和生化评估、急性与延迟反应以及环境触发因素,该研究提高了模型的有效性,并加深了对CM相关反应的理解。

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