Abstract
Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects of testosterone propotionate on skeletal muscle using rat model of sepsis. Male SD rats were randomly divided into experimental group, model control group, sham operation group and blank control group. Rats in experimental group were given testosterone propionate two times a week, 10 mg/kg for 3 weeks. Maximal contraction force, fatigue index and cross-sectional area of the extensor digitorum longus (EDL) were measured. Myosin, IGF-1, p-AKT and p-mTOR levels in EDL were detected by Western blot. Histological changes of the testis and prostate were detected by hematoxylin and eosin staining. We found that maximal contraction force and fatigue index of EDL in experimental group were significantly higher than in model control group. Cross-sectional area of fast MHC muscle fiber of EDL in group was significantly higher than in model control group. The levels of myosin, IGF-1, p-AKT and p-mTOR of EDL in experimental group were significantly higher than in model control group. In addition, no testicle atrophy and prostate hyperplasia were detected in experimental group. In conclusion, these results suggest that testosterone propionate can significantly improve skeletal muscle strength, endurance and volume of septic rats, and the mechanism may be related to the activation of IGF-1/AKT pathway. Moreover, testosterone propionate with short duration does not cause testicular atrophy and prostate hyperplasia in septic rats. Therefore, testosterone propionate is a potential treatment for muscle malfunction in ICUAW patients.
Highlights
Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients who have decreased muscle strength and weakened peripheral nerve excitability. [1] At present, it is generally believed that the occurrence of ICUAW is related to multiple factors, including sepsis, multi-organ failure and mechanical ventilation, among which sepsis is the most prominent [2]
Body weight of rats in experimental group and model control group significantly decreased compared with sham group and blank control group on the 8th day after surgery before testosterone treatment (P < 0.01), and there was no significant difference between experimental group and model control group
The fatigue index of extensor digitorum longus (EDL) was significantly higher in experimental group than in model control group, while it was significantly higher in sham operation group and blank control group than in model control group (Figure 2C)
Summary
Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients who have decreased muscle strength and weakened peripheral nerve excitability. [1] At present, it is generally believed that the occurrence of ICUAW is related to multiple factors, including sepsis, multi-organ failure and mechanical ventilation, among which sepsis is the most prominent [2]. Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients who have decreased muscle strength and weakened peripheral nerve excitability. ICUAW affects approximately 40% of critically ill patients, and even 50–100% patients with severe sepsis [3]. Prevention and treatment of ICUAW have become an urgent medical issue [4]. Testosterone is a major male hormone applied in clinical practice in elderly men and patients with severe burns and other weaknesses to improve muscle function and quality of life [5]. Testosterone improved the muscle function of paraplegia, limb fracture and castration [6,7]. Determining whether the appropriate testosterone supplements can be given to ICUAW patients need further studies
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