Experimental study on the anti-inflammatory mechanism of Guipi decoction on myasthenia rats after chemotherapy
Objective:To investigate the anti-inflammatory mechanism of Guipi decoction in improving chemotherapy-induced myasthenia based on the results of network pharmacology and bioinformatics analysis.Methods:Forty SPF male SD rats were ran-domly divided into the blank group,the model group,the Guipi decoction low-dose,medium-dose and high-dose groups with 8 rats in each group according to random number table method.5-Fluorouracil(28 mg/kg)was intraperitoneally injected for 5 consecu-tive days to establish a chemotherapy-induced muscle weakness model.Guipi decoction at low,medium and high dose were admin-istrated by gavage(0.5,1,2 g/mL)for 14 consecutive days.The body weight and grip strength of each group were recorded,and the expression of reactive oxygen species(ROS)in gastrocnemius tissues was detected by immunofluorescence.The expressions of hypoxia-induced-factor 1α(HIF-1α)protein in gastrocnemius was detected by immunohistochemistry.The expression of inflam-matory factors IL-1β,IL-6,TNF-α,chemokine receptors CCR1,CCR2,CCR7,CXCR-4 and TNF-family receptors TNFR1 and TRAF6 in gastrocnemius were detected by Western blot.Results:Compared with the control group,the body weight and grip strength of rats in the model group were significantly decreased(P<0.01).ROS production in gastrocnemius was significant-ly increased(P<0.01).Immunohistochemistry results showed that HIF-1α expression was increased(P<0.01).The expressions of IL-1β,IL-6,TNF-α,CCR1,CCR2,CCR7,CXCR-4,TNFR1 and TRAF6 were significantly increased(P<0.01).Com-pared with the model group,ROS production in gastrocnemius of low,medium and high dose Guipi decoction groups was signifi-cantly decreased(P<0.01),while the expressions of HIF-1α were significantly increased(P<0.01).The expressions of IL-1β,IL-6,TNF-α,CCR1,CCR2,CCR7,CXCR-4,TNFR1 and TRAF6 were significantly decreased(P<0.05).Conclusion:Gui-pi decoction may inhibit the level of intramusculature inflammation and induce the activation of HIF-1α to combat the oxidative stress caused by inflammation,so as to alleviate the muscle weakness caused by chemotherapy.
ChemotherapyMyastheniaGuipi decoctionInflammationTNF family receptorsChemokine receptors
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