Role of mitochondrial damage during cardiac apoptosis in septic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.</p><p><b>METHODS</b>Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.</p><p><b>RESULTS</b>Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.</p><p><b>CONCLUSIONS</b>Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.</p>

No association between 3 polymorphisms of transforming growth factor beta3 gene and essential hypertension in Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied.</p><p><b>RESULTS</b>Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms.</p><p><b>CONCLUSIONS</b>Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.</p>