RESUMEN
Diabetic neuropathy pain (DNP), a spontaneous pain with hyperalgesia and allodynia, greatly compromises patients' quality of life. Our previous study suggested that dexmedetomidine (DEX) can relieve hyperalgesia in rats by inhibiting inflammation and apoptosis at the level of the spinal cord. In the present study, we aimed to evaluate the role of Wnt 10a/ß-catenin signaling in DEX-induced alleviation of DNP in rats. Forty-eight rats were randomly allocated to four groups (n=12/group): control, DNP, DEX, and yohimbine groups. The DNP model was established by streptozotocin (STZ) injection. The effects of DEX with or without the α 2 adrenergic antagonist yohimbine were assessed by behavior tests (mechanical withdrawal threshold and thermal withdrawal latency). Spinal cord tissue was evaluated by immunofluorescence staining of astrocytes as well as for Wnt 10a and ß-catenin expression, western blot analysis of Wnt 10a and ß-catenin expression, and enzyme-linked immunosorbent assay measurement of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß). Rats with STZ-induced DNP had a decreased pain threshold, activated astrocytes, increased expression of Wnt 10a and ß-catenin, and increased levels of proinflammatory cytokines compared to the control group, and these effects were ameliorated by treatment with DEX. Yohimbine administration partly abolished the protective effects of DEX in the DNP model rats. In conclusion, DEX alleviated DNP in rats by inhibiting inflammation and astrocyte activation, which may be attributed to downregulation of the Wnt 10a/ß-catenin signaling pathway.
Asunto(s)
Astrocitos , Dexmedetomidina/farmacología , Nefropatías Diabéticas , Neuralgia , Proteínas Wnt/biosíntesis , Vía de Señalización Wnt/efectos de los fármacos , Animales , Astrocitos/metabolismo , Astrocitos/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/prevención & control , Regulación de la Expresión Génica , Masculino , Neuralgia/metabolismo , Neuralgia/patología , Neuralgia/prevención & control , Ratas , Ratas Sprague-Dawley , beta Catenina/biosíntesisRESUMEN
We first report a novel ß chain variant, Hb Heze [ß144(HC1)LysâArg; HBB: c.434A>G], in a Chinese family. Heterozygous inheritance of the mutation results in a mild ß-thalassemia (ß-thal) phenotype, whereas compound heterozygosity of Hb Heze with ß0-thal appears as the cause of ß-thal intermedia (ß-TI) in our case.
Asunto(s)
Pueblo Asiatico/genética , Hemoglobinas Anormales/genética , Mutación , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética , Alelos , Sustitución de Aminoácidos , China , Codón , Análisis Mutacional de ADN , Índices de Eritrocitos , Femenino , Genotipo , Humanos , Masculino , Linaje , Fenotipo , Talasemia beta/sangreAsunto(s)
Muestra de la Vellosidad Coriónica , Retardo del Crecimiento Fetal/genética , Pruebas Genéticas , Proteínas con Homeodominio LIM/genética , Mutación , Factores de Transcripción/genética , Regiones no Traducidas 3' , Aborto Eugénico , Adulto , Sustitución de Aminoácidos , China , Composición Familiar , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/metabolismo , Asesoramiento Genético , Heterocigoto , Humanos , Proteínas con Homeodominio LIM/química , Proteínas con Homeodominio LIM/metabolismo , Medida de Translucencia Nucal , Embarazo , Primer Trimestre del Embarazo , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Secuenciación del ExomaRESUMEN
The double heterozygosity for α and ß chain variants leads to the formation of abnormal heterodimer hybrids, which could render laboratory diagnostics in a routine setting difficult. The following is the first report of a double heterozygosity for Hb Q-Thailand [α74(EF3)AspâHis; HBA1: c.223G>C] with α+-thalassemia (α+-thal) and Hb J-Bangkok [ß56(D7)GlyâAsp; HBB: c.170G>A] found in a Chinese family. Both subjects were healthy with normal or borderline hematological parameters. Hemoglobin (Hb) analyses showed a novel variant, Hb Q-Thailand and Hb J-Bangkok. Family studies helped in the initial recognition and in making presumptive diagnoses, but definitive diagnoses of these cases with complex α and ß chain variants could only be obtained after DNA analysis.
