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Aim To observe the effects of benazepril and irbesartan on myocardial collagen in chronic heart failure ( CHF ) rats and the possible mechanisms. Methods CHF model in rats was made by partially banding abdominal aorta to induce pressure overload cardiac hypertrophy. The rats were given benazepril or/and irbesartan for 8 weeks. Systolic blood pressure ( SBP) was monitored by rat tail artery. The ultrastruc-ture of myocardium was detected by transmission elec-tron microscope. The content of myocardial hydroxyproline and amount of cross-linked collagen were measured by hydrolysis method. The expression of type Ⅰ and Ⅲ collagen protein in myocardium was investigated by immunohistochemistry. The expression of p-38 MAPK and p-p38 MAPK proteins was detected by Western blot. Results Compared with the model of CHF, there was no significant difference in SBP af-ter treatment. The content of hydroxyproline in myocar-dium, degree of cross-linked collagen, as well as ex-pression of type I collagen, type Ⅲ collagen and p-p38 MAPK proteins were significantly decreased after treatment with benazepril or irbesartan ( P <0. 05 ) , and the combined treatment of them had better effects. Conclusion There is a synergistic effect of attenua-ting the quantity and quality of myocardial collagen in CHF rats by combined use of benazepril and irbesar-tan, which may be related to the down regulation of p-p38MAPK protein expression.
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<p><b>OBJECTIVE</b>To investigate the time course of let-7a microRNA expression in the cell cycle of HeLa cells.</p><p><b>METHODS</b>HeLa cells were synchronized in G(1), S and G(2)/M phases using double-thymidine block, and the cell cycle phases were defined by flow cytometry. Real-time quantitative RT-PCR was used to examine the expression of let-7a in HeLa cells in different cell cycle phases.</p><p><b>RESULTS</b>The synchronization rates of G(1), S and G(2)/M phases were 84.81%, 83.65% and 77.69%, respectively. Let-7a was constitutively expressed throughout the cell cycle in HeLa cells, but the expression levels in G(1) and S phases were lower than those in G(2)/M phase.</p><p><b>CONCLUSIONS</b>Cell cycle can significantly influence the expression level of let-7a, which may provide new clues to the understanding of the cell cycle control mechanisms.</p>
Subject(s)
Humans , Cell Cycle , Genetics , Gene Expression Regulation, Neoplastic , Physiology , HeLa Cells , MicroRNAs , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of microRNA on the gene expression profile of human leukemia K562 cells using microarray technique.</p><p><b>METHODS</b>miR-181a RNA duplexes were designed and synthesized according to the mature sequence of miR-181a. Forty-eight hours after transfection of in vitro cultured K562 cells using Oligofectamine, gene expression profiles of the cells were studied and analyzed using Agilent Human 1A Oligo microarray.</p><p><b>RESULTS</b>Totalling 228 differentially expressed genes were identified from the 20,173 screened genes, including 59 up-regulated ones (consisting of metabolism-associated genes, tumor suppressor genes, signal transduction-associated genes, immunity and defense-associated genes etc), and 169 down-regulated ones (consisting of oncogenes, DNA-binding and transcription genes, metabolism-associated genes, signal transduction-associated genes, cell cycle and development-associated genes etc.) in the transfected K562 cells as compared with the control K562 cells. Changes in expressions of CTCF, ZAP70, SEMA4C and RALA were confirmed by semi-quantitative reverse transcription-polymerase chain reaction.</p><p><b>CONCLUSIONS</b>miR-181a transfection for 48 h induces gene expression profile changes in K562 cells, indicating the functionality of the miR-181a. These differentially expressed genes are related to the functions of the microRNA, and may also be the basis of the regulation model of posttranscriptional gene silencing. These findings provide an evidence for further study of the machineries and functions of the microRNA in mammalian cells.</p>
Subject(s)
Humans , Gene Expression Profiling , K562 Cells , MicroRNAs , Genetics , Oligonucleotide Array Sequence Analysis , RNA, Small Interfering , Genetics , TransfectionABSTRACT
Objective To study the anti-oxidative stress effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril(10 mg/kg?d,n=9)or candesartan(4 mg/kg?d,n=9)or combina- tion(Ben:10 mg/kg?d+Can:4 mg/kg?d)for 12 weeks.The tail arterial pressure was measured every two weeks.At end of study,pathological changes in the thoracic aorta,activity of SOD,serum contents of NO and hydroxy radicals,plasma Ang Ⅱ and cGMP,eNOS and P22~(phox)protein expressions in aortic tunica intima were de- termined.Results The thoracic aorta wall was thickened markedly in SHRs,and blood pressure,hydroxy radi- cal,Ang Ⅱ and P22~(phox)protein expression were increased significantly,while the serum NO,level of cGMP and eNOS expression were decreased.Benazepril(Ben)or Candesartan(Can)inhibit the thickening of vessel wall, enhance the activity of SOD(Ben:68.7?2.1,Can:65.6?4.2 vs SHR:48.8?3.2 U/mL,P
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Aim To investigate the myocardial hypertrophy,the expression of transforming growth factor ?1(TGF-?1),Smad3 and Smad7 proteins in spontaneous hypertensive rats(SHR)and the effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril and candesartan for 12 weeks.The tail arterial pressure was measured every two weeks.At 12 th weekend,cardiac configuration,heart mass index,area of cadiocytes,concertrations of AngⅡin plasma and myocardium,expressions of TGF-?1、Smad3 and Smad7 proteins were measured respectively.Results The arterial pressure,wall thickness,heart mass index,area of cardiocytes and the expressions of TGF-?1,Smad3 proteins increased in SHRs but were attenuated after the treatment of benazepril or candesartan.After the combined treatment,the synergistic effect could be observed.The levels of cardiac tissue and plasma AngⅡwere reduced.The expressions of Smad 7 were up-regulated after the treatment of benazepril or candesartan,while they were stable after the combined use.Conclusion There is a synergistic effect of attenuating myocardial hypertrophy in SHRs by combined use of benazepril and candesartan.It may be related to the regulation of Ang Ⅱ,decreasing the expressions of TGF-?1 and Smad3.