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Métodos Terapéuticos y Terapias MTCI
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1.
Br J Pharmacol ; 169(6): 1352-71, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23647015

RESUMEN

BACKGROUND AND PURPOSE: Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes. In this study we investigated whether TXNIP is involved in type 1 diabetes-associated NAFLD and whether antioxidants, quercetin and allopurinol, alleviate NAFLD by targeting TXNIP. EXPERIMENTAL APPROACH: Diabetes was induced in male Sprague-Dawley rats by a single i.p. injection of 55 mg · kg⁻¹ streptozotocin. Quercetin and allopurinol were given p.o. to diabetic rats for 7 weeks. Hepatic function, oxidative stress, inflammation and lipid levels were determined. Rat BRL-3A and human HepG2 cells were exposed to high glucose (30 mM) in the presence and absence of antioxidants, TXNIP siRNA transfection or caspase-1 inhibitor, Ac-YVAD-CMK. KEY RESULTS: Quercetin and allopurinol significantly inhibited the TXNIP overexpression, activation of NLRP3 inflammasome, down-regulation of PPARα and up-regulation of sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, fatty acid synthase and liver X receptor α, as well as elevation of ROS and IL-1ß in diabetic rat liver. These effects were confirmed in hepatocytes in vitro and it was further shown that TXNIP down-regulation contributed to the suppression of NLRP3 inflammasome activation, inflammation and changes in PPARα and SREBPs. CONCLUSIONS AND IMPLICATIONS: Inhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes-associated NAFLD.


Asunto(s)
Alopurinol/uso terapéutico , Antioxidantes/uso terapéutico , Proteínas Portadoras/antagonistas & inhibidores , Diabetes Mellitus Tipo 1/complicaciones , Hígado Graso/prevención & control , Hígado/efectos de los fármacos , Quercetina/uso terapéutico , Alopurinol/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Antioxidantes/farmacología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Línea Celular , Suplementos Dietéticos , Hígado Graso/complicaciones , Hígado Graso/metabolismo , Hígado Graso/patología , Silenciador del Gen , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Masculino , Terapia Molecular Dirigida , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo/efectos de los fármacos , Quercetina/administración & dosificación , Quercetina/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo
2.
Zhongguo Zhen Jiu ; 33(11): 993-5, 2013 Nov.
Artículo en Chino | MEDLINE | ID: mdl-24494286

RESUMEN

OBJECTIVE: To observe the difference in the efficacy on traumatic nerve injury among electroacupuncture, warm needling therapy and electroacupuncture plus warm needling therapy and explore the better therapeutic method. METHODS: The electromyography (EMG) and electroneurography (ENG) of 93 cases showed traumatic nerve injury of moderate damage. According to the single blind randomization principle, they were divided into an electroacupuncture (EA) group, a warm needling therapy (WN) group and an EA plus WN group, 31 cases in each one. The main acupoints were selected from Yangming Meridian and Shaoyang Meridian corresponding to the distribution of damaged nerves. EA, WN and EA plus WN were applied separately. The treatment was given once every day, 15 treatments made one session. After 3 sessions of treatment (45 treatments in total), EMG and ENG were re-checked and the results were analyzed statistically. RESULTS: Regarding the total effective rate and effective rate, it was 96. 8% (30/31) in the EA plus WN group, which was better than 74.2% (23/31) in the EA group and 77. 4% (24/31) in the WN group (P<0. 05). Concerning to the improvements of EMG, the result in the EA plus WN group was 96.8% (30/31), which was better than the other two groups [74. 2%(23/31),74. 2%(23/31)] (P<0. 05). In terms of the recovery of nerve conduction and amplitude, the results in EA plus WN group [(50.9+/-4. 6)m/s,(8. 8+/-2. 9),microVx1 000] were better than the other two groups [(43.7+/-3.1)m/s,(4. 2+/-1. 9)microV X 1 000,(43. 8+/-3. 3)m/s,(4. 5+/-2. 2)microV X 1 000] (P<0. 05). CONCLUSION: EA combined with WN is a better therapy of acupuncture and moxibustion in the treatment of traumatic nerve injury.


Asunto(s)
Terapia por Acupuntura , Traumatismos de los Nervios Periféricos/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
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