1.Role of histone acetylation modification imbalance in regulation of cardiac hypertrophy induced by phenylephrine
Chang PENG ; Xiaomei LUO ; Shuo LI ; Huichao SUN
Chinese Journal of Pathophysiology 2017;33(2):227-232
[ ABSTRACT] AIM: To investigate the regulatory mechanism of histone acetylation on cardiac hypertrophy in -duced by phenylephrine , and to provide a new idea for preventing and curing hypertrophic cardiomyopathy .METHODS:Phenylephrine was given by continuous subcutaneous injection for modeling cardiac hypertrophy in C 57BL/6 mice.The le-vel of histone H3 lysine 27 acetylation (H3K27ac) in the promoter of cardiac nuclear transcription factor GATA4 and the mRNA expression of GATA4 were identified by chromatin immunoprecipitation (ChIP) and real-time PCR, respectively. Meanwhile, the protein expression of histone H3K27ac, atrial natriuretic peptide (ANP) and α-myosin heavy chain (α-MHC) was determined by Western blot .Cardiac hypertrophy in the mice was observed by HE staining and echocardio-graphy.RESULTS:The results of Western blot showed that the level of histone H 3K27ac in phenylephrine group was sig-nificantly increased compared with normal saline group (P<0.05), and ChIP-qPCR data showed that the level of histone H3K27ac in the promoter of GATA4 was increased significantly in the same samples (P<0.05).The expression levels of GATA4 mRNA and ANP protein in phenylephrine group were apparently increased compared with normal saline group ( P<0.05).However, histone acetylase inhibitor anacardic acid attenuated histone H 3K27 hyperacetylation induced by pheny-lephrine, and downregulated the over-expression of GATA4 and ANP in the heart of the mice (P<0.05).HE staining and echocardiography data showed that phenylephrine apparently increased left ventricular posterior wall thickness and de -creased left ventricular end-systolic diameter and left ventricular end-diastolic diameter , while anacardic acid also reversed these indexes that mentioned above and attenuated cardiac hypertrophy induced by phenylephrine in the mice .CONCLU-SION:Histone acetylation modification imbalance is involved in cardiac hypertrophy induced by phenylephrine , and the histone acetylase inhibitor anacardic acid decreases histone hyperacetylation induced by phenylephrine and attenuates car -diac hypertrophy in the mice .
7.Suberoylanilide Hydroxamic Acid Improves Cardiac Hypertrophy via Inhibiting Histone Deacetylase in Experimental Mice
Chang PENG ; Shuo LI ; Xiaomei LUO ; Xinxing XIE ; Mingchen XIAO
Chinese Circulation Journal 2017;32(8):803-807
Objective: To explore the effect of suberoylanilide hydroxamic acid (SAHA) improving cardiac hypertrophy via inhibiting histone deacetylases (HDAC) in experimental mice and to provide a new idea for prevention and treatment of cardiac hypertrophy. Methods: Cardiac hypertrophy mice model was established by thoracic aorta ligation. A total of 60 Kunming mice were randomly divided into 4 groups: Normal control group, Sham operation group, Cardiac hypertrophy (CH) group and CH+SAHA group. There were 6 mice used in each group. Myocardial cell morphology was observed by HE staining, cardiac function was assessed by echocardiography, mRNA and protein expressions of HDAC5 (the isoform of HDAC) and β-MHC were examined by RT-PCR and Western blot analysis. Results: The mice in CH group had myocardial cell hypertrophy, disordered arrangement and hyperchromatic nucleus. Compared with Sham operation group, CH group showed decreased left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic volume (LVEDV) and increased thickness of inter-ventricular septum (IVS), allP<0.05; CH group presented elevated mRNA and protein expressions of HDAC5 and β-MHC,P<0.05. SAHA obviously decreased HDAC5 expression, down regulated cardiac hypertrophy related β-MHC gene expression, improved cardiac function and hypertrophy, all P<0.05. Conclusion: HDAC were involved in myocardial hypertrophy; SAHA could inhibit HDAC expression and therefore,improved myocardial hypertrophy in experimental mice.
8.Clinical Analysis and Mechanism Study of Conditioning of Postoperative Endometrial Carcinoma in Staging Ⅰ with Integrated Traditional Chinese and Western Medicine
Xintao SU ; Xiufang WANG ; Quanxiang LI ; Shuo LUO
International Journal of Traditional Chinese Medicine 2008;30(6):458,460-
Objective To investigate if the anticancer prescription Fuzhengyiaitang in combination with progestogen matching chems can have better clinical effects than progestogen alone.Methods Collecting 60 patients and grouped into two randomly.One group named the experimental group and the other is named the control.The experimental group is given Fuzhengyiaitang and progestogen and the control ine is given the progestogen alone.The clinical effects are investigated.Results The experimental group had better clinical effects than the other one and the results had statistical significance.The experimental group are stronger,had better immunal functions and less side effects.Conclusion Fuzhengyiaitang and progestogen match cbems Can have better clinical effects in treating the stage I's operation.
9.Growth and secretion features of microencapsulated human adrenal pheochromocytoma cells in artificial cerebrospinal fluid
Xiao LI ; Xinsheng ZHANG ; Haijie LUO ; Shuo LUAN ; Qing WAN ; Shaoling WU ; Chao MA
Chinese Journal of Tissue Engineering Research 2015;(38):6114-6120
BACKGROUND:Microencapsulated cels are commonly used as a tool to overcome immune rejection after subarachnoid transplantation. However, the effect of microencapsulation on the secretion of human pheochromocytoma cels is unclear.
OBJECTIVE:To observe the growth and secretion of primarily microencapsulated cultured human pheochromocytoma cels in artificial cerebrospinal fluid.
METHODS: The human pheochromocytoma tissues were digested successively to isolate human pheochromocytoma cels that were then cultured in artificial cerebrospinal fluid. Primary cels were covered with alginate-polylysine-alginate microcapsules, and then the cel morphology was observed with inverted phase contrast microscope. Levels of met-enkephalin and norepinephrine in cel culture medium were detected by enzyme-labeled immunosorbent assay (ELISA). We used cel counting kit-8 colorimetric assay to obtain the growth curve of human pheochromocytoma cels in artificial cerebrospinal fluid.
RESULTS AND CONCLUSION:Microcapsulated human pheochromocytoma cels were in suspension and the process outgrowth increased slowly. Compared with non-microcapsulated cels, the proliferation rate of microcapsulated cels increased significantly. ELISA results revealed a significant increase in the levels of met-enkephalin and norepinephrine secreted from the microencapsulated cels compared to the non-microcapsule group. There was a wide variation in contents of met-enkephalin and norepinephrine from different tumors. These findings indicate that microencapsulated human pheochromocytoma cels can survive wel and have good secretion function in artificial cerebrospinal fluid, and human pheochromocytoma cels from different tumor tissues have stable secretory function.
10.Implanted main portal venous tumor thrombus model in experimental rabbits:its establishment and evaluation
Wen ZHANG ; Shuo LI ; Zhiping YAN ; Jianjun LUO ; Qingxin LIU ; Xudong QU ; Jianhua WANG
Journal of Interventional Radiology 2015;(9):801-806
Objective To establish a stable animal model of implanted main portal vein tumor thrombus (MPVTT) in rabbits and to evaluate its usefulness in research so as to provide the basis for clinical treatment. Methods Twenty-four New Zealand white rabbits were randomly divided into group A (control group,n=10) and group B (study group,n=14). For the rabbits of the study group, a sac-like pouch was sewed up in the anterior wall of the main portal vein, and then the tumor slice was injected into the portal vein through the pouch and it was hung and fixed on the inner wall of the main portal vein with the help of the reserved suture. For the rabbits of the control group, only a sac-like pouch was sewed up in the anterior wall of the main portal vein after opening the abdomen. After the treatment, the animals were kept under observation on the general condition, body weight and survival time. Postoperative multi-slice spiral CT scan was performed once a week to check the growth of portal vein tumor thrombus and the metastasis. The experimental rabbits were separately sacrificed for pathologic examination, the volume of MPVTT was determined and the metastasis was evaluated. The survival time of the remaining rabbits were analyzed. Results The tumor formation rate of the study group was 100%. The mean body weight of the rabbits of the study group (No.9-No.14 rabbits) and the control group at 35 days after the procedure was (1.48±0.19) kg and (2.08 ±0.17) kg respectively. The mean survival time of the study group (No.9-No.14 rabbits) was (41.7 ±4.72) days. Multi-slice spiral CT scan revealed MPVTT, metastasis and collateral circulation due to portal vein obstruction. Pathological examination confirmed the presence of thrombus in the portal vein and metastasis . Conclusion Stable MPVTT in animal models that can be used for imaging evaluation are successfully established. This study proves that multi-slice spiral CT scan is of great value in diagnosing and monitoring the growth of MPVTT and metastasis, which provides useful basis for clinical research and treatment of MPVTT.