RESUMO
【Objective】 To investigate the effects of formononetin (FMN) on cardiomyocyte apoptosis and HSP90/AKT in rats with dilated cardiomyopathy-mediated heart failure. 【Methods】 Echocardiography, ELISA, histological staining, and TUNEL staining were used to observe the protective effect of different doses of FMN on dilated cardiomyopathy-mediated heart failure in rats and the apoptosis of cardiomyocytes. The potential targets of formononetin on dilated cardiomyopathy-mediated heart failure were obtained from TCMSP, DisGeNet, GeneCards, and other databases, the key targets were obtained according to the protein-protein interaction (PPI) network, and the key targets were verified by molecular docking. Western blotting was used to further verify the regulatory role of key targets in the treatment of dilated cardiomyopathy-mediated heart failure with formononetin. 【Results】 Formononetin could reduce the levels of LVIDS, LVIDD, NT-pro BNP, cTn-T, CK, CK-MB, and LDH in rats with dilated cardiomyopathy-mediated heart failure, increase the levels of EF and FS, and reduce the apoptosis of cardiomyocytes. FMN had a strong binding effect on 10 key targets (AKT1, HSP90AA1, CASP3, MAPK1, MMP9, SRC, ALB, HRAS, IGF1, and EGFR) screened by network pharmacology, with HSP90AA1 and AKT1 having the strongest binding effect. Formononetin decreased the expression of HSP90, AKT and downstream CASP3 protein, but increased the expression of p-AKT in myocardial tissue. 【Conclusion】 Formononetin may inhibit the expression of HSP90, promote phosphorylation of AKT to p-AKT, and inhibit the expression of CASP3, thereby reducing the apoptosis of cardiomyocytes and improving myocardial tissue damage, so as to achieve the purpose of treating dilated cardiomyopathy-mediated heart failure.
RESUMO
Objective:To explore the effect of Rehmanniae Radix combined with Scrophulariae Radix on renal microinflammation in diabetic nephropathy (DN) rats. Methods:50 Sprague Dawley (SD) rats were adaptively fed for 1 week, and then 10 rats were randomly selected as the blank control group, and the rest were treated with STZ intraperitoneal injection combined with high-fat diet to induce DN model. After 4 weeks, the successful modeled rats were randomly divided into model group, Rehmannia glutinosa Scrophularia group (5.25 g/kg) and metformin group (200 mg/kg), with 10 rats in each group. After 8 weeks of administration, fasting blood glucose was measured by blood glucose meter; microalbuminuria was measured by benzalkonium chloride turbidimetry; serum cystatin, TNF-α, IL-6 and hs-CRP levels were measured by ELISA kit; renal pathological changes were detected by HE staining, Masson staining and PAS staining; the expression of MCP-1, NF-κB (total) and p-NF-κB protein in renal tissue was detected by Western blot.Results:Compared with the model group, the body weight of rats in DHXS group was significantly decreased ( P<0.05). The content of fasting blood glucose[(18.06 ± 5.69) mmol/L vs. (29.42 ± 0.63)mmol/L], 24-hour urine protein [(11.02 ± 1.77)mg/d vs. (31.61 ± 0.65)mg/d], serum cystatin [(208.16 ± 12.07)ng/ml vs. (278.05 ± 19.33)ng/ml], TNF-α [(9.13 ± 1.46)pg/ml vs. (73.16 ± 8.30)pg/ml], IL-6[(4.27 ± 1.07)pg/ml], hs-CRP[(219.36 ± 22.02)ng/ml vs. (266.97 ± 15.80)ng/ml] in DHXS group were significantly decreased ( P<0.05), and the expression level of p-NF-κB (0.49 ± 0.07 vs. 0.84 ± 0.12) and MCP-1 (0.44 ± 0.02 vs. 0.64 ± 0.11) in renal tissue of rats in DHXS group were significantly reduced ( P<0.05). Conclusion:Rehmanniae Radix combined with Scrophulariae Radix can protect kidney by inhibiting the over activation of NF-κB, and reducing the expression of MCP-1 related protein to reduce renal micro inflammation.