[Clinical effect of Shenfu injection combined with glucocorticoid on patients with acute left heart failure complicated with bronchospasm].

OBJECTIVE: To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm. METHODS: A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded. RESULTS: Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment. CONCLUSIONS: Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.

Circular RNA ITCH mediates H2O2-induced myocardial cell apoptosis by targeting miR-17-5p via wnt/ß-catenin signalling pathway.

Cardiovascular disease is a severe threat health worldwide, and circRNAs have been shown to be correlated with the development of cardiovascular disease. Expression of circ-ITCH and miR-17a-5p was evaluated by RT-qPCR. Cell viability was measured using CCK-8. Flow cytometry was applied to measure apoptosis rate. Binding between miR-17-5p and circ-ITCH was detected via luciferase reporter assays. Levels of ATP in cells were examined with ATP testing. Western blot was used to evaluate apoptosis-related proteins and proteins in Wnt/ß-catenin signalling pathway. H2O2 induced apoptosis of H9c2 cells and lowered cell viability as well as ATP levels and circ-ITCH expression. After overexpression, circ-ITCH enhanced cell viability and ATP concentration. Meanwhile, apoptosis was inhibited. MiR-17-5p was the target of circ-ITCH as evidenced by luciferase report assays, with higher expression in H2O2-induced H9c2 cells. Knockdown of miR-17-5p could promote cell viability and level of ATP and curb apoptosis and p53 and PARP expression. Moreover, overexpressed miR-17-5p could reverse the function of upregulated circ-ITCH. Wnt3a, Wnt5a and ß-catenin in Wnt/ß-catenin signalling pathway were increased after H2O2 induction. Suppression of Wnt/ß-catenin signalling pathway could initiate the process of injury in H9c2 cells. Circ-ITCH could protect myocardial cells from injuries caused by H2O2 by suppressing apoptosis while miR-17-5p played a reverse role, which could upregulate apoptosis and inhibit cell viability via Wnt/ß-catenin signalling pathway.

The role of the rat sarcoplasmic reticulum Ca2+-ATPase promoter in myocardial ischemia-preconditioning.

Intracellular calcium ion concentration ([Ca2+]i) is a key regulator of ischemia-reperfusion injury (IRI) and ischemic preconditioning (IPC), with myocardial sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) acting as the major regulatory protein in the control of [Ca2+]i. In this study, we examined the effect of the SERCA2a promoter in IRI and IPC. The SERCA2a promoter fragment was acquired using PCR and molecular cloning technology, and was inserted into a luciferase reporter gene vector to construct reporter gene plasmids. Primary cultured neonatal rat cardiomyocytes were treated by analog ischemic treatment to produce in vitro models of IRI and IPC. Using an in vitro gene transfer assay, SERCA2a transcriptional activity was measured under conditions of IRI and IPC. Results from this study showed that (1) short duration analog ischemia treatment (analog IPC) results in a significant decrease in transcriptional activity, (2) analog IRI caused a dramatic depression in SERCA2a gene expression in transcription initiation levels, and (3) analog IPC attenuated IRI-induced transcriptional depression, even though IPC itself significantly depressed transcriptional activity. In conclusion, the SERCA2a promoter plays a significant role in IRI and IPC, with IPC able to precondition the SERCA2a promoter against the deleterious effects of IRI-induced injury.

[Sarcolemmal sodium-calcium exchanger mediated the beneficial effects of myocardial ischemic preconditioning and pharmacological preconditioning].

OBJECTIVE: To investigate the role of sodium-calcium exchanger (NCX) on ischemic preconditioning and pharmacological preconditioning. METHODS: Cultured rat neonatal cardiomyocytes were randomly divided into 6 groups: (1) ischemia/reperfusion group (9 h ischemia followed by 1 h reperfusion, I/R), (2) ischemic preconditioning group (1.5 h ischemia/1 h reperfusion + I/R), (3) pharmacologic preconditioning group, adenosine (10 micromol/L) pretreated for 1 h + I/R, (4) calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (0.5 micromol/L for 0.5 h) + ischemic preconditioning group, (5) KN-93 + pharmacologic preconditioning group, (6) control group. The leakage of intracellular lactate dehydrogenase (LDH) in various groups was determined by biochemical autoanalyzer. Semi-quantitative RT-PCR was employed to measure the mRNA levels of sodium-calcium exchanger. Activity of sodium-calcium exchanger (Na(+)-dependent (45)Ca(2+) uptake) was measured by liquid scintillation counting. RESULTS: (1) Compared to the I/R group, the LDH leakages in both ischemic preconditioning group and pharmacologic preconditioning group were significantly reduced (P < 0.05) while significantly increased in the KN-93 + pharmacologic preconditioning group and the KN-93 + ischemic preconditioning group (P < 0.05). (2) The Na(+)-dependent (45)Ca(2+) uptake was significantly increased in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05). (3) The expression of NCX mRNA in I/R group was also significantly increased (P < 0.05) in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05), CaMKII inhibitor KN-93 significantly abolished these effects in preconditioning group (P < 0.05) and in adenosine pretreated group (P < 0.05). CONCLUSION: NCX mediated the cardioprotective effects of ischemic preconditioning and pharmacological preconditioning in the neonatal cardiomyocytes I/R model.