1.Study of mechanism and inhibition of botulinum toxin type A on hypertrohic scar fibroblasts
Xue ZHANG ; Dong LAN ; Shuhua NING ; Liwei RAN ; Hongxia JIA ; Sisi YU ; Xiaojun WANG
Chongqing Medicine 2017;46(5):580-582,585
Objective To explore the mechanism and inhibition of botulinum toxin type A (BTXA) on hypertrohic scar fibroblasts.Methods The cells were treated by 0 (control),0.2,0.4,0.8 U/ml BTXA for 48 h.Cell viability was detected by MTT assay.Cell apoptosis was detected by Hoechst staining.Cell cycle was detected by flow cytometry.The level of cell cycle related protein D1 (Cyclin D1),proliferation nuclear antigen (PCNA) and activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) signaling pathway were assayed by western blot.Results Compared with control group(0.75±0.07),0.2,0.4,0.8 U/mL BTXA(0.59 ± 0.06,0.43 ± 0.04,0.34± 0.03) inhibited hypertrohic scar fibroblasts cell viability,increased cell apoptotic rate[control group(2.38±0.24)%;BTXA(15.79±1.54)%,(27.32±2.69)%,(38.46±3.90)%],down-regulated the expression of Cyclin D1(control group 1.57±0.18;BTXA 0.93±0.07,0.42±0.04,0.35±0.03) and PCNA(control group 1.46±0.16;BTXA 0.50±0.05,0.59±0.05,0.37±0.03),inhibited the expression of PI3K(control group 0.98±0.06;BTXA 0.49±0.04,0.50±0.04,0.39±0.03) and the phosphorylation of AKT(control group 1.38±0.08;BTXA 0.97±0.06,0.60±0.04,0.29± 0.02),made cell cycle arrested in G1 phase,The difference was statistically significant (P<0.05).Conclusion These results suggested BTXA inhibit proliferation via blocking the activation of PI3K/AKT signal pathway and down-stream related cell cycle related protein.
2.Gene expression profiling and functional analysis of cerebral artery after experimental subarachnoid hemorrhage
Ning GAN ; Qin PAN ; Sisi LIU ; Ke REN ; Shuai ZHOU ; Haiqing DONG ; Zhaoyan SONG ; Yi WANG
Tianjin Medical Journal 2017;45(4):355-358
Objective To explore the difference of gene expression profiling between normal basilar arteries and basilar arteries of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rabbits. Methods cDNA chip of normal basilar arteries and basilar arteries of CVS after SAH in rabbits were downloaded from GEO database. The chip was analyzed and screened by Bioconductor software, and function enrichment and pathway analysis of the differentially expressed genes were analyzed by Cytoscape software. Then 6 adult male Japanese rabbits were used, and randomly divided into normal control group (n=3) and SAH model group (n=3). Rabbit SAH models were established by cisterna secondary-blood-injection method. RNA data of normal basilar artery specimens on the 0 day and basilar artery specimens after SAH on the 5-day were used to validate the parts of differentially expressed genes by qRT-PCR. Results A total of 4356 differentially expressed genes were found in normal basilar arteries and basilar arteries of CVS after SAH in rabbits. Among them, 920 genes were considered to be significant with P-value<0.05, such as GRIK1, MYH13, ZNF45, SAA3, RLN1, MSR1 and others. Function enrichment analysis indicated that the differentially expressed genes were involved in regulation of Ca2+transmembrane transporter activity, negative regulation of ion transmembrane transport, regulation of potassium ion transport, positive regulation of JAK-STAT signaling cascades and other biological processes. Pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and other signaling pathways maybe related with the differentially expressed genes. qRT-PCR verification showed that the expression of MSR1 in SAH model group was consistent with that of the chip result. Conclusion The gene expressions of basilar arteries of CVS after SAH in rabbits are significantly different, and MSR1 gene can be used as a potential target for studying the pathological mechanism of CVS.
3. Controversies over the targets of controlling blood pressure in hypertensive patients with chronic kidney disease
Sisi NING ; Yuhong ZHAO ; Lei YAN ; Minna TANG ; Ningzhi ZHANG ; Yongqiao ZHANG ; Zhaoqiang CUI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):463-467
The increasing incidence of chronic kidney disease (CKD) has become a major global public health problem. Hypertension and CKD can cause and effect each other and often coexist. Controlling blood pressure is one of the core tasks in the treatment of CKD. Over the past 10 years, many large clinical studies have provided evidence-based medical evidence for the updating and revision of hypertension management guidelines, but there remains controversies in targets of blood pressure in hypertensive patients with CKD. Personalized and evidence-based management is the key to achieve effective control of blood pressure and slow the progression of CKD. This review will summary the epidemiological status of hypertensive patients with CKD and the progress related to the targets of controlling blood pressure in CKD.
4. Application of chronopharmacology in the hypertension treatment
Ningzhi ZHANG ; Minna TANG ; Yongqiao ZHANG ; Sisi NING ; Zhaoqiang CUI ; Yuhong ZHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(4):418-422
The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.