Protective effect and mechanism of Panax notoginseng saponins myocardial targeting lipo-somes on endotoxemic myocardial injury mice
Objective:To observe the cardioprotective effect of Panax notoginseng saponins myocardial target-ing liposomes(PAC-L-PNS)on mice with endotoxemic myocardial injury and explore the possible mechanism.Methods:Fifty male C57BL/6J mice were randomly divided into normal,model,PAC-L-PNS,normal liposomes of PNS(L-PNS)and PNS groups,with 10 mice in each group.The PAC-L-PNS,L-PNS and PNS groups were in-jected with corresponding drugs in the tail vein,respectively.The mice in the normal and model groups were in-jected with the same volume of blank liposomes in the tail vein for 5 days,and 4 h after the last dose,mice in the normal group were intraperitoneally injected with saline,and mice in the other groups were intraperitoneally in-jected with lipopolysaccharide(LPS,10 mg/kg)to establish a myocardial injury model.Mice were executed 12 hours after modeling,TUNEL staining and HE staining were used to observe the apoptosis of cardiomyocytes and histopathological changes of myocardium in each group;the activities of creatine kinase(CK)and lactate de-hydrogenase(LDH)in serum were detected by detector;the contents of IL-6,IL-1β,TNF-α and MCP-1 in serum were detected by enzyme-linked immunosorbent assay(ELISA);the mRNA expression of NF-κB P65,IκBα,TLR4 and IRAK1 in mouse myocardial tissues were determined by reverse transcription-quantitative polymerase chain reaction(RT-qPCR);in addition,vascular irritation and hemolytic assays were performed to preliminarily evaluate the safety of PAC-L-PNS.Results:PAC-L-PNS was virtually free of hemolytic and vascular irritation phenomena and was biocompatible.Compared with the normal group,the apoptosis rate of cardiomyocytes was significantly higher in the model group mice(P＜0.01),and myocardial tissue injury was more severe.Compared with the model group,mice in the PAC-L-PNS and L-PNS groups had significantly fewer myocardial apoptotic cells(P＜0.01)and improved histopathology,and there was no significant difference in mice in the PNS group.Compared with the normal group,CK,LDH activity,IL-6,IL-1β,TNF-α,and MCP-1 content,TLR4,IRAK1,NF-κB P65,and IκBα mRNA expression were significantly elevated in mice in the model group(P＜0.01).Com-pared with the model group,CK,LDH activity,content of each inflammatory factor,TLR4,IRAK1,NF-κB P65,and IκBα mRNA expression were significantly lower in mice in the PAC-L-PNS group(all P＜0.05).CK activity,content of each inflammatory factor,TLR4,and IRAK1 mRNA expression were significantly decreased in the PAC-L-PNS group compared with the L-PNS and PNS groups(all P＜0.05).Conclusion:PAC-L-PNS has a sig-nificant protective effect on LPS-induced endotoxemic myocardial injury,and its mechanism may be related to the inhibition of inflammatory factor production and attenuation of cardiac tissue lesions.
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