Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

OBJECTIVE:To investigate the effects of levocarnitine on peripheral blood T cell subsets and inflammatory factors in diabetic patients underwent peritoneal dialysis. METHODS:A total of 100 diabetic patients underwent peritoneal dialysis in se-lected as research objects were divided into conventional therapy group and levocarnitine group according to random number table, with 50 cases in each group. Conventional therapy group received peritoneal dialysis and conventional therapy. Levocarnitine group was additionally given levocarnitine 1.0 g added into 0.9% Sodium chloride injection 20 mL intravenously,3 times a week,on the basis of conventional therapy group for 12 weeks. CD3+,CD4+,the proportion of Th1 and Th2,the contents of TNF-α,INF-γ, IL-10 and IL-4 in supernatant were all detected before and after treatment. The expression of T-bet and GATA-3 were compared be-tween 2 groups. RESULTS:After treatment,CD3+,CD4+,Th2 cells,GATA-3 expression and IL-10,IL-4 levels were significantly increased,the expression of Th1 cells,T-bet content and TNF-αand INF-γwere significantly reduced,and levcarnitine group was sig-nificantly better than conrentional therapy group,with statistically significant (P<0.05). CONCLUSIONS:Levocarnitine can im-prove inflammatory reaction and the expression of related transcription factors by promoting T cell subsets and Th1/Th2 cell subsets.

Objective To explore the relationship of peritoneal transport patterns and the nutritional status in continuous ambu-latory peritoneal dialysis(CAPD) patients .Methods 89 patients who took CAPD in 2010 January to December 2012 in the perito-neal dialysis center of our hospital were selected in this study .According to the ratio of creatinine in peritoneal dialysis solution and in blood(D/Pcr)of the peritoneal equilibrium test(PET) ,all CAPD patients were divided into HA group(high average transport) and LA group(low average transport) .Nutritional status including serum albumin(ALB) ,prealbumin(PA) ,transferrin(TF) ,hemo-globin(Hb) ,Lean body mass(LBM) ,subjective global assessment(SGA)and normalized Protein Equivalent of Nitrogen Appearance (nPNA) were compared in both groups .The relationship of D/Pcr and the nutritional status were analyzed .Results D/Pcr in HA group were significantly higher than in LA group(P<0 .01) .ALB ,PA ,TF ,Hb and SGA in HA group were significantly higher than in LA group(P<0 .01) ,but nPNA in two groups has no statistical differences (P>0 .05) .D/Pcr was negative related to ALB , TF ,Hb and SGA(P<0 .01) ,but not related to nPNA ,PA and LBM (P>0 .05) .Conclusion The nutritional status is related to peritoneal transport patterns in peritoneal HA patients ,it is necessary to strengthen nutritional guidance ,as the nutritional status is worse compared to LA ones .