[Screen absorption enhancer for intranasal administration preparations of paeoniflorin based on nasal perfusion method in rats].

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-ß-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

Identification of apoptosis-related microRNAs and their target genes in myocardial infarction post-transplantation with skeletal myoblasts.

BACKGROUND: Skeletal myoblasts (SkMs) has provided a promising treatment for myocardial infarction (MI). Functioning as posttranscriptional regulators, microRNAs (miRNAs) play important roles in cardiac repairment and stem cell regulation. However, the correlation between miRNAs and their targeted genes in SkM cell therapy for MI was not fully understood. METHODS: We explored the cardioprotection by SkMs in infracted rats and determined cardiac functions at 4 weeks. In addition, we compared the expression profiles of miRNAs and mRNAs in post-MI rats with or without SkM cell therapy using microarray. The concordance between miRNA expression and mRNA levels of potential target genes was confirmed by quantitative real-time PCR. RESULTS: Quantitative echocardiography and histology showed improved cardiac function, attenuated heart infarcted area and inhibited cardiomyocyte apoptosis in the SkM group, compared with MI group. We identified that 160 miRNAs were differentially expressed in MI group as compared to the control group and 78 miRNAs were differentially expressed in the SkM treated group as compared to the untreated post-MI. We focused on a novel set of apoptosis-associated miRNAs and their target genes, among which 4 miRNAs (miR-30a-5p, miR-30c-5p, miR-145-5p, miR-140-3p), except one (miR-143-3p), were downregulated in the SkM treated group as compared to the untreated group. Furthermore, we found seven genes including Angptl4, Dpep1, Egr1, Eif5a, Tsc22d3, Irs2 and Cebpb that showed a linear correlation with which miRNAs. CONCLUSIONS: The downregulation of apoptosis-regulatory miRNAs and in turn upregulation of target genes may partially account for rescue effect of SKM therapy for MI.

Andrographolide inhibits intimal hyperplasia in a rat model of autogenous vein grafts.

The saphenous vein is considered a common conduit for coronary artery bypass grafting. A major limitation involved is the high graft occlusion rate. We evaluated the effect and mechanism of andrographolide on intimal hyperplasia (IH) of autografted rat veins. For this purpose, 140 female Sprague-Dawley rats were randomly divided into experimental (andro) and control groups. Andro rats received andrographolide (200 mg/kg) lavaged once daily for 2 days before surgery while controls received normal saline. The external jugular vein was grafted into the ipsilateral carotid artery. The animals were killed at 1/3 days and 1/2/4/6/8 weeks postoperatively. The neointima to media area (I/M) ratio was determined. Expression of the p65, E-selectin and MMP-9 proteins/mRNA was also determined. Autografted rat veins displayed IH postoperatively. In andro rats, compared with controls, IH was significantly reduced (P < 0.01) at 2/4/6/8 weeks but not at 1/3/7 days postoperatively. Andrographolide also significantly (P < 0.05) reduced the expression of E-selectin and MMP-9 proteins/mRNAs at 2/4/6/8 weeks postoperatively whereas p65 protein/mRNA was significantly (P < 0.05) diminished at 1/3 days and 1/2/4/6/8 weeks postoperatively as compared with controls. Therefore, it was concluded that andrographolide inhibited IH in autografted rat veins through the suppression of p65, E-selectin, and MMP-9 at the transcriptional level.