Mechanism Of Ginsenoside Rb1 In Improving Inflammatory Response And Muscle Atrophy In Postoperative Fatigue Model Rats

Objectives: Postoperative fatigue syndrome(POFS)is a common clinical complication after operation,especially major abdominal surgery.Patients who underwent POFS would feel much anxiety,depression,sleep insufficiency,concentration difficulty,muscular weakness and debilitating fatigue.Fatigue after surgery was associated with systemic inflammation,and patients with more intense inflammatory responses after surgery experienced more persistent fatigue than patients suffering from a less level of inflammation.However,the pathogenesis of postoperative fatigue syndrome has not been fully elucidated.Previous studies have found that ginsenoside Rb1(Gbenoside Rb1,GRb1)can improve oxidative stress level and energy metabolism of skeletal muscle,and can improve central inflammation in rats with postoperative fatigue syndrome.Therefore,our study aimed to investigate the effects of ginsenoside Rb1 on skeletal muscle inflammation and atrophy in postoperative fatigue syndrome rats.Methods: Rats were randomly divided into 3 groups:(1)control group,(2)model group,(3)model + ginsenoside Rb1(GRb1)group.Rats in the GRb1 group were treated with GRb1(15 mg / kg)intraperitoneally every day from the 3 days before surgery until the day of sacrifice,once a day.Rats in the control group and the model group were administrated with physiological saline in the same manner.Through the open field test,the rod fatigue test and the grip test,the spontaneous activity level,muscle coordination level and muscle strength were detected.The serum levels of inflammatory cytokines IL-1β,IL-6 and TNF-α were detected by ELISA.The inflammatory cytokines IL-1β,IL-6 and TNF-α in the gastrocnemius was detected by real-time reverse transcription polymerase chain reaction(q RT-PCR).The phosphorylation levels of p38 and NF-κB and the expression levels of murf1 and atrogin-1 in the gastrocnemius muscle of each group were detected by Western Blot.The ultrastructure of the gastrocnemius muscle was observed by transmission electron microscopy.Inflammatory infiltration in the gastrocnemius muscle was assessed by HE staining and immunohistochemistry.Results: On the 1st,3rd,and 7th day after surgery,the behavioral experiments showed that in the model group the spontaneous activity level decreased,the grip strength decreased,and the balance coordination ability decreased.GRb1 significantly increased the spontaneous activity level,muscle strength and muscle coordination in POFS rats.The expression levels of IL-1β,IL-6 and TNF-α in serum and muscle of the model group were increased by ELISA and q RT-PCR.The levels of IL-1β,IL-6 and TNF-α in serum and muscle of GRb1 group were significantly decreased.WB results showed that the phosphorylation levels of p38 and NF-κB in the model group were increased,the protein expression levels of murf1 and atrogin-1 were increased.And the phosphorylation levels of p38 and NF-κB in the GRb1 group were decreased,the protein expression levels of murf1 and atrogin-1 are decreased.Rats treated with GRb1 had lower levels of inflammatory infiltration compared to the model group by HE staining and immunohistochemistry.In addition,the morphology of the myofilament of the GRb1 group was better than that of the model group by transmission electron microscopy.Conclusions: In conclusion,we observed that ginsenoside Rb1 significantly improved skeletal muscle function in POFS rats through behavioral tests.The inflammatory response and atrophy of skeletal muscle may be related to the mechanism of POFS.Ginsenoside Rb1 may inhibit the inflammatory response and reduce the skeletal muscle atrophy by inhibiting the p38MAPK-NF-κB signaling pathway.Ginsenoside Rb1 has anti-fatigue effect on post-operative fatigue model rats,and it is likely to be a potential drug to accelerate postoperative recovery.Further clinical studies are needed to explore the safety and effectiveness of GRb1 in clinical use.