| 1.Purpose To observe the effect of Shenqi Jianxin formula on chronic HF model rats with coronary artery ligation,and to explore the protective mechanism of Shenqi Jianxin formula on CHF by studying the inflammatory response and TNF-α/NF-κB signaling pathway.2.MethodsSeventy SPF male SD rats were divided into sham-operated group(n=8)and modeling group(n=62),and the modeling group was subjected to left coronary artery ligation to construct a post-infarction heart failure rat model,while the sham-operated group was only threaded.4 weeks later,the successful preparation of the model was judged,and the modeling group was randomly divided into MODEL group(MODEL group),Ginseng-Qi Jianxin Fang group(SQJXF group),Shakubarat(SKB)group(SQJXF group),and SQJXF group(SQJXF group).(SQJXF+SKBQ group),and SQJXF+Pyrrolodithiocarbamate group(SQJXF+PDTC group).Drug intervention began at the end of the fourth week.SQJXF group were given clinical administration of Shenqi Jianxin formula(7.4mg/kg/d).SQJXF+PDTC group were given intraperitoneally injected PDTC solution(100mg/Kg/d)and clinical administration of Shenqi Jianxin formula(7.4mg/kg/d).SKBQ group was given Shakubactril valsartana calcium tablets(68 mg/kg/d);SQJXF+SKBQ group was given Shenqi Jianxin formula(7.4mg/kg/d)and Shakubactril valsartan calcium tablets(68 mg/kg/d);the blank group and MODEL group were given equal amounts of saline(15 ml/kg/d).One drug intervention was performed at 8 am every day for a total of 4 weeks.Detection index:(1)The general growth and death of rats were recorded periodically during gavage.(2)BW,HW and LVW of rats were recorded at the end of 8 weeks,and heart mass index(CL=HW/BW)and left ventricular mass index(LVMI=LVW/BW)were counted.(3)ELISA was performed to detect the levels of serum N-terminal pro-brain natriuretic factor(NT-pro BNP),interleukin-6(IL-6),tumor necrosis factor-a(TNF-α),transforming growth factor β1 protein(TGF-β1)and nuclear transcription factor p65(NF-κB p65)in rats.(4)Western Blot to detect the levels of IL-6,TNF-α,TGF-β 1,human phosphorylated-nuclear transcription factor-κB-p65(p-NF-κB p65)protein in rats.(5)IL-6,TNF-α,TGF-β1,type Ⅰ collagen(Collagen1),type Ⅲ collagen(Collagen3)and nuclear transcription factor p65(NF-κB p65)were detected by RT-PCR.(6)HE and Masson staining to detect myocardial pathological status in mice.3.Results(1)General observation: During the whole experiment,the rats in the sham operation group had healthy mental state,free movement,sensitive response,healthy food and water intake,dense and glossy fur,and obvious weight gain.After 4 weeks of modeling,MODEL group rats gradually showed mental malaise,reduced exercise,fatigue and lethargy,poor eating,cyanosis of mouth,yellow hair,serious hair shedding,diarrhea,symptoms and signs such as subcutaneous edema and weight loss,and showed a progressive worsening trend,and these symptoms became more obvious at the 8th week.After 4 weeks of continuous administration of each drug intervention group,compared with the MODEL group,the rats showed different degrees of symptom relief,body weight was significantly increased,hair was visible,response sensitivity,mental activity and diet were still possible,among which the SQJXF+SKBQ group and SQJXF+PDTC group had the most obvious efficacy.(2)Rat body BW,HW,LVW,CL(HW/BW),LVMI(LVW/BW)results: compared with the sham-operated group,the MODEL group had reduced body weight,increased heart mass,increased left ventricular mass,and significantly increased HW/BW and LVW/BW ratios,and the differences were statistically significant(P < 0.05);compared with the MODEL group,the rats in each administration group had Compared with the MODEL group,the rats in the SQJXF+PDTC group had increased body weight,decreased heart mass,decreased left ventricular mass,and significantly decreased HW/BW and LVW/BW ratios,and the differences were statistically significant(P <0.05);compared with the SQJXF group,the weight of rats in SQJXF+PDTC group increased while their heart mass and left ventricular mass decreased.The ratios of HW/BW and lvw/BW decreased significantly,and the difference was statistically significant(P<0.05).(3)Serum NT-pro BNP,IL-6,TNF-α,TGF-β1,NF-κBp65 results in rats: compared with the sham-operated group,the levels of NT-pro BNP,IL-6,TNF-α,TGF-β1,NF-κ Bp65 were significantly higher in the MODEL group,and the differences were statistically significant(P < 0.05).Compared with the MODEL group,the levels of NT-pro BNP,IL-6,TNF-α,TGF-β1,and NF-κBp65 were significantly lower in each administration group,and the difference was statistically valuable(P < 0.05).Compared with the SQJXF group,the levels of NT-pro BNP,IL-6,TNF-α,TGF-β1,NF-κBp65were significantly lower in the SQJXF+PDTC group,and the differences were statistically valuable(P < 0.05).(4)Myocardial IL-6,TNF-α,TGF-β1,p-NF-κB p65 protein results in rats: compared with the sham-operated group,IL-6,TNF-α,TGF-β1,p-NF-κB p65 protein levels were significantly increased in the MODEL group,and the differences were statistically significant(P < 0.05).Compared with the MODEL group,the levels of IL-6,TNF-α,TGF-β1,and p-NF-κB p65 protein in the SKBQ group,SQJXF+SKBQ group,and SQJXF+PDTC group rats were significantly reduced,and the differences were statistically significant(P < 0.05),and the levels of IL-6,TGF-β1,and p-NF-κB p65 protein in the SQJXF group The levels of IL-6,TGF-β1,and p-NF-κB p65 proteins were also significantly lower in the SQJXF group,and the differences were statistically significant(P < 0.05),but the differences in TNF-α protein content were not statistically significant(P > 0.05).Compared with the SQJXF group,IL-6,TNF-α,TGF-β 1 and p-NF-κ B p65 protein levels were also significantly lower in the SQJXF+PDTC group,and the differences were statistically significant(P < 0.05).(5)Results of IL-6,TNF-α,TGF-β1,Collagen1,Collagen3,NF-κB p65 levels in rats:compared with the sham-operated group,IL-6,TNF-α,TGF-β 1,Collagen1,Collagen3,NF-κB p65 levels in rats in the MODEL group were significantly increased,and the differences were statistically significant(P < 0.05).Compared with the MODEL group,the contents of IL-6,TNF-α,TGF-β1,Collagen1,Collagen3 and NF-κB p65 were significantly decreased in each administration group,and the difference was statistically significant(P < 0.05).Compared with SQJXF group,IL-6,TNF-α,TGF-β 1,Collagen1,Collagen3,NF-κ B p65 contents were significantly lower in SQJXF+PDTC group rats,and the difference was statistically significant(P < 0.05).(6)HE staining results: The morphology and structure of the myocardium in the sham operation group were intact,the arrangement was regular,and no clear injury or inflammatory cell infiltration was observed.The MODEL group showed obvious myocardial cell swelling,unclear structure,disordered arrangement,uneven myocardial fiber staining,intercellular hyperplasia,a large number of inflammatory cell infiltration,and obvious tissue injury.Compared with MODEL group,myocardial tissue lesions in other administration groups were significantly improved,myocardial cells were arranged in an orderly manner,and inflammation was significantly relieved.Among them,myocardial pathological changes were most obvious in SQJXF+SKBQ group and SQJXF+PDTC group,which were similar to sham operation group.(7)Masson staining results: No abnormal collagen fibers were found in myocardial cells of rats in the sham operation group.In the MODEL group,a large area of myocardial collagen fiber deposition and myocardial fibrosis were observed;compared with the MODEL group,the area of myocardial fiber distribution was reduced and the degree of myocardial fibrosis was improved in each administration group,among which the SQJXF+SKBQ group and SQJXF+SKBQ group and SQJXF+PDTC group showed little difference in pathological changes compared with the sham-operated group.4.Conclusion:(1)Ginseng and Astragalus can alleviate the symptoms and signs,reduce the heart weight index and left ventricular mass index,and improve myocardial tissue lesions,and the combination of traditional Chinese medicine and western medicine was superior to single traditional Chinese medicine or western medicine..(2)Shenqi Jianxin can reduce the level of NT-pro BNP in chronic heart failure rats,improve heart function,effective prevention and treatment of chronic heart failure.(3)Shenqi Jianxin can reduce the levels of IL-6,TNF-α,TGF-β1 inflammatory cytokines in chronic heart failure rats,reduce the myocardial tissue and systemic inflammatory response,protect myocardial cells,and improve ventricular hypertrophy.(4)Shenqi Jianxin can reduce the levels of Collagen1 and Collagen3 proteins in myocardial tissue of rats with chronic heart failure and effectively inhibit abnormal excessive deposition of collagen1 and Collagen3 protein,and thus improve myocardial fibrosis and ventricular remodeling.(5)Shenqi Jianxin can improve myocardial pathological changes in chronic heart failure rats,relieve inflammation,improve myocardial fibrosis,reduce myocardial cell injury and necrosis rate,and protect myocardial cells.(6)Shenqi Jianxin formula has a protective effect on myocardial cells in rats with chronic heart failure.The mechanism may be that by inhibiting TNF-α /NF-κ B signaling pathway,it can reduce the process of myocardial fibrosis,reverse ventricular remodeling,and improve cardiac function,so as to play a protective effect on HF. |
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