Effects of Shexiangbaoxin pills on the expression of cardiac α₁- and β-adrenergic receptor subtypes in rat hearts with heart failure induced by myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic heart failure (CHF) had been characterized as an activated sympathetic system leading to the alteration of adrenergic receptor (AR) levels in the heart. Thus far, not much research has been done with regard to traditional Chinese medical treatment for CHF. We investigated the effect of Shexiangbaoxin pills (SXBXP) on the function of the heart and the expression of a(1)-AR and b-AR subtypes in the messenger RNA (mRNA) levels and protein levels of non-infarction left ventricular tissue from rats with CHF induced by myocardial infarction.</p><p><b>METHODS</b>Models of CHF were established by left anterior descending coronary artery ligature. Fifty-four Wistar rats were randomly divided into five groups: normal control group (group A), sham operation group (group B), CHF model group (group C), positive medicine control group (group D), and small-dose SXBXP group (group E) and large-dose SXBXP group (group F), deployed intragastrically. Cardiac function was examined by echocardiography before and after therapy; mRNA expressed levels were measured by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) for b(1)-AR, b(2)-AR, b(3)-AR, a(1A)-AR, a(1B)-AR, and a(1D)-AR; protein levels were measured by Western blotting analysis for b(1)-AR, b(2)-AR, a(1A)-AR, a(1B)-AR, and a(1D)-AR in non-infarction left ventricular tissue.</p><p><b>RESULTS</b>There was no significant difference in the left ventricular ejection fraction (LVEF) between groups A and B. Compared to group B, LVEF of groups C, D, E, and F were significantly decreased (P < 0.01) before therapy. After therapy, compared to group C, LVEF of group F was significantly improved (P < 0.05). Compared to group B, b(1)-AR and a(1B)-AR expressed levels were markedly decreased (P < 0.05), a(1A)-AR and b(3)-AR were significantly increased (P < 0.01) in group C, and in both mRNA and protein expressed levels b(2)-AR had no significant difference between groups B and C (P > 0.05). a(1D)-AR mRNA levels were unchanged in each group (P > 0.05), but a(1D)-AR protein level was significantly decreased in group C (P < 0.05). After treatment, compared to group C, mRNA levels of b(1)-AR and a(1B)-AR were significantly increased (P < 0.05 and P < 0.01), and a(1A)-AR was markedly decreased in groups D, E, and F (P < 0.05). b(3)-AR level significantly declined in both groups D and F (P < 0.01), but b(2)-AR and a(1D)-AR expressed levels remained unchanged in each group (P > 0.05). Protein levels, compared to group C, b(1)-AR was significantly increased (P < 0.01, P < 0.05, and P < 0.01) and a(1A)-AR was markedly decreased in groups D, E, and F (P < 0.05, P < 0.01, and P < 0.01). b(2)-AR expressed level was significantly increased in group F (P < 0.05). a(1B)-AR expressed level was significantly increased in both groups E and F (P < 0.05), and a(1D)-AR was remarkably increased in both groups D and F (P < 0.05).</p><p><b>CONCLUSIONS</b>After SXBXP treatment, LVEF was increased and cardiac function was significantly ameliorated in rats with CHF. The therapeutic effect of SXBXP may be related to better blood supply for myocardium and up-regulation of b(1)-AR and a(1B)-AR, and down-regulation of a(1A)-AR and b(3)-AR. The results show that SXBXP can be used in treatment of CHF and the therapeutic effect of large-dose SXBXP is superior to small-dose SXBXP.</p>

p16INK4a expression mediated by recombinant adenovirus can induce senescence of A549 cells / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To construct E1-deletion and replication-defective human type 5 recombinant adenovirus vector and to study the effect of p16INK4a on proliferation and aging of A549 cells.</p><p><b>METHODS</b>p16INK4a cDNA was cloned into pAdCMV to construct recombinant pAdCMV p16INK4a, which was co-transfected into 293 cell together with pJM17. The recombinant p16INK4a adenovirus (Ad-p16INK4a) was generated by homologous recombination and identified with duplex PCR. Lung cancer cell A549, which has a homozygous deletion of p16INK4a gene, was infected with the prepared Ad-p16INK4a virus. X-gal staining and TRAP-ELISA were used for detecting senescence-associated beta-galactosidase and telomerase activities in A549 cells.</p><p><b>RESULTS</b>Immunohistochemical staining and Western blot indicated that p16INK4a gene was transferred into A549 cell with more than 95% efficiency by recombinant adenovirus and p16INK4a protein was expressed at a high level- p16INK4a could markedly inhibit growth of A549 cells, induced expression of senescence-associated beta-galactosidase and suppressed telomerase activity in A549 cells.</p><p><b>CONCLUSION</b>Recombinant adenovirus vector could efficiently mediate transfer and expression of foreign genes in human cell and could be used for gene immunization and gene therapy; p16INK4a could inhibit A549 cell growth and induce its replicative senescence.</p>