RESUMO
Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial , Quinases Associadas a rho/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Dinaminas/genética , Dinaminas/metabolismo , GTP Fosfo-Hidrolases , Hipoglicemiantes/uso terapêutico , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The association of the single nucleotide polymorphism 301T>C in the coding region of the acylation-stimulating protein (ASP) gene with coronary heart disease (CHD) was investigated in the Uygur (385 CHD patients and 483 control subjects) and Han (390 CHD patients and 439 control subjects) populations of China. The frequency of the CC and CT genotypes was significantly higher in patients with CHD compared to the control group (55.3 vs 46.2%, P = 0.001) in the Uygur population, but in the Han population, the frequency was significantly higher in the control group (51.7 vs 24.4%, P < 0.001). In addition, the C allele was significantly associated with CHD in the Uygur population (C allele: 33.8 vs 26.2%, T allele: 66.2 vs 73.8%; P = 0.004) and in the Han population (C allele: 14.5 vs 30.3%, T allele: 85.5 vs 69.7%; P < 0.001). The CC genotype was independently associated with increased risk of coronary artery disease when adjusted for other cardiovascular risk factors [odds ratio (OR) = 2.189, 95% confidence interval (CI) = 1.251-3.830, P = 0.001] in the Uygur population, but was a protective factor for CHD in the Han population (OR = 0.373, 95%CI = 0.187-0.745, P = 0.005). In conclusion, the 301T>C polymorphism of the ASP gene that influences the serum triglycerides level in the Uygur population, is associated with the development of CHD, and the CC genotype might be a risk factor of CHD.
Assuntos
Complemento C3a/genética , Doença das Coronárias/genética , Predisposição Genética para Doença , Triglicerídeos/sangue , Acilação/genética , Idoso , Povo Asiático/genética , China , Doença das Coronárias/sangue , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We aimed to investigate the relationships between polymorphisms of the glutathione S-transferases (GSTs) GSTM1, GSTTI, and GSTP1 and the risk of developing acute myeloid leukemia (AML). A total of 206 AML cases and 231 controls were collected for our study. The genotyping of GSTs (GSTM1, GSTTI, and GSTP1) was based upon the duplex polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) method. Individuals carrying null GSTTI and GSTM1 genotypes had a 1.52- and 1.78-fold increased risk of developing acute leukemia, respectively, compared to non-null genotype carriers (P < 0.05). A high risk was observed in those carrying a combination of null genotypes of GSTM1 and GSTTI with GSTP1-Val allele genotypes when compared with those carrying wild-type genotypes, with an odds ratio (95% confidence interval) of 3.62 (1.53-8.82) (P < 0.05). These findings indicate that genetic variants of GSTTI and GSTM1 significantly increase the risk of developing AML. Our study offers important insights into the molecular etiology of AML.
Assuntos
Predisposição Genética para Doença , Glutationa Transferase/genética , Leucemia Mieloide Aguda/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
C5L2, a G protein-coupled receptor, is known to be a functional receptor of acylation-stimulating protein, which is a stimulator of triglyceride synthesis and glucose transport. A novel C5L2 variant (S323I) was identified and its association with familial combined hyperlipidemia (FCH) was recently reported. We looked for this SNP in three Chinese ethnic groups, including Han, Uygur, and Kazakh controls and patients with FCH and type 2 diabetes. One hundred and eighty-two unrelated subjects (77 of Han, 57 of Uygur, and 48 of Kazakh) with FCH were genotyped by direct sequencing, and 852 subjects (342 of Han, 338 of Uygur, 172 of Kazakh) with type 2 diabetes and 200 healthy controls (67 of Han, 72 of Uygur, and 61 of Kazakh) chosen from a cardiovascular risk survey study were genotyped with PCR-RFLP analysis. All 182 subjects with FCH, 99.5% of the type 2 diabetes patients and 100% of the healthy controls were successfully genotyped. Neither the FCH subjects nor the type 2 diabetes patients were found to have the S323I variant. This variant was also not identified in the healthy controls. We found no evidence to demonstrate that the S323I polymorphism contributes to familial combined hyperlipidemia or type 2 diabetes in the Chinese population.
Assuntos
Povo Asiático , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Hiperlipidemia Familiar Combinada/genética , Polimorfismo de Nucleotídeo Único , Receptores de Quimiocinas/genética , Adulto , Idoso , Alelos , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , China/epidemiologia , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Hiperlipidemia Familiar Combinada/complicações , Hiperlipidemia Familiar Combinada/etnologia , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Receptor da Anafilatoxina C5a , Fatores de Risco , Serina/genéticaRESUMO
The extensive nucleotide sequence heterogeneity among independent genotypes of wild polioviruses permits the systematic design of genotype-specific molecular reagents. We have prepared two sets of polymerase chain reaction (PCR) primer pairs specific for the genotype of wild poliovirus type 3 recently endemic to Mexico and Guatemala. Nucleotide sequences of a representative wild type 3 virus isolated in Mexico in 1989 differed from the corresponding Sabin 3 (Leon 12 a1b) sequences at 167 of 900 positions within the VP1 region. From the sequence data, wild virus-specific primer pairs were designed to complement regions of high mismatch (greater than 33%) with Sabin 3 templates. Primer binding sites were spaced along the genome so that the predicted amplification products (142 bp and 163 bp) could be easily resolved electrophoretically from the products generated with our Sabin strain-specific primers (Sabin 1: 97 bp; Sabin 2: 71 bp; Sabin 3: 53 bp). RNAs of all wild type 3 poliovirus isolates from Mexico and Guatemala obtained over a 13-year period (1977-1990) served as efficient templates for amplification of the 142-bp and 163-bp products. Genomic templates derived from vaccine-related polioviruses and most heterologous wild polioviruses were inactive under equivalent reaction conditions. Amplifications generating a 114-bp product with a broadly reacting primer pair, matching highly conserved sequences in the 5'-noncoding region, provided a positive control for the presence in samples of poliovirus (or enterovirus) RNAs. Selective amplification of wild Mexico-Guatemala type 3 poliovirus sequences was obtained with either primer set in reactions containing large stoichiometric excesses (up to 10(6)-fold) of vaccine-related RNAs. We have used wild genotype-specific PCR primer sets to facilitate identification of wild polioviruses present in both clinical and environmental samples.