[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

The relationship between trophoblast differentiation and the production of bioactive hCG.

We previously showed that a significant number of failing pregnancies are associated with production of human chorionic gonadotropin (hCG) having relatively low bioactivity. The present study was designed to compare the secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during trophoblast differentiation, and to test the hypothesis that the lower bioactive: immunoreactive hCG ratios in failing pregnancies are related to reduced or impaired trophoblast differentiation. Cytotrophoblast cells were isolated from term placentas and cultured under conditions that induced or did not induce syncytiotrophoblast formation. Culture media were collected at regular intervals up to 72 h and levels of immunoreactive and bioactive hCG were measured. The differentiation of cytotrophoblast cells to multinucleated syncytiotrophoblast was monitored by immunocytochemistry and electron microscopy. During the 72 h culture period, concentrations of immunoreactive and bioactive hCG increased in both differentiating and non-differentiating cells. However, the concentrations of immunoreactive and bioactive hCG were higher under culture conditions that promoted trophoblast differentiation. Furthermore, the ratio of bioactive hCG to immunoreactive hCG was higher in differentiating cultures. When differentiation was inhibited by dimethyl sulfoxide, the secretion of bioactive hCG was reduced and the bioactive: immunoreactive hCG ratio did not change. These findings are consistent with the idea that production of bioactive hCG accompanies syncytiotrophoblast formation.