RESUMO
AIMS: Nerve growth factor (NGF), a member of the neurotrophin family, plays an essential role in diabetic neuropathy and ischemic heart disease. In the present study, we explored the potential role of NGF and the involvement of TRPV1 receptor in isolated diabetic mouse hearts following ischemia/reperfusion (I/R) injury. METHODS: Adenovirus-mediated NGF gene delivery was performed on diabetic and sham hearts 8weeks after streptozotocin treatment. The sciatic nerve conduction velocity was recorded using a biological signal acquisition system. Forty-eight hours after heart surgery, mice were subjected to I/R injury using a Langendorff system. Several cardiac parameters and the expression of associated molecules were analyzed during the experiment. RESULTS: The sciatic nerve conduction velocity was reduced in diabetic mice compared with that in control mice. Decreased expression of NGF, TRPV1, and the downstream neurotransmitters CGRP and SP was observed in the diabetic hearts. Adenovirus-mediated NGF overexpression reversed the reduction in TRPV1 and downstream neuropeptides, resulting in improved cardiac recovery post-I/R injury in diabetic hearts. The protective effect of NGF was abolished by CGRP8-37 (a selective CGRP antagonist), while it was preserved by low-dose capsaicin. CONCLUSIONS: The NGF-induced up-regulation of TRPV1 via the increased synthesis and release of endogenous CGRP leads to improved cardiac performance in I/R-injured diabetic heart.
Assuntos
Diabetes Mellitus Experimental/genética , Cardiomiopatias Diabéticas/genética , Coração/fisiopatologia , Isquemia Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/genética , Fator de Crescimento Neural/fisiologia , Canais de Cátion TRPV/genética , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/reabilitação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/reabilitação , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/reabilitação , Fator de Crescimento Neural/genética , Transdução de Sinais/genética , Estreptozocina , Canais de Cátion TRPV/metabolismo , Regulação para Cima/genéticaRESUMO
A 31-year-old female was admitted with headache, memory disturbance, abnormal behavior, incontinence, confusion, complex partial seizures, decreased oxygen saturation and increased temperature. Anti-NMDAR antibodies were positive in serum and cerebrospinal fluid. Subsequently, a regimen of immunotherapy that included intravenous immunoglobulins, methylprednisolone, plasma exchange and their combinations were used. But the treatment was ineffective. Though both transvaginal ultrasonography and abdominal CT scan contrast revealed left ovarian cyst, the patient had left oophorectomy. And during surgery we found a small cyst mass contained fat-like liquid with air in her left ovarian. Pathological examination demonstrated mature cystic teratoma accompanied with brain tissue. She has made gradual and steady improvement after surgery, but not fully recovery. By combining this case with previous studies of others, we further discuss the clinical characteristics, treatment and prognosis of the disease.