RESUMO
Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological properties. In this article, the effects of UA on apoptosis and the proliferation of human hepatoma Huh-7 cells were reported. The MTT results showed that cell viability of Huh-7 was reduced in a concentration and time-dependent effect. In addition, DAPI staining was used to detected condensation of chromatin in nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The results showed that exposure to UA affected extrinsic and intrinsic pathways through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the apoptotic proteins TNF-α, Fas, FADD, and Bax; and activation of cleaved caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling transduction pathways, and increased activity in the p-ERK signaling pathway. Taken together, UA inhibited the cell growth of Huh-7 cells and affected apoptosis, via regulated cellular signaling transduction.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estrutura Molecular , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Triterpenos/química , Proteína Tumoral 1 Controlada por Tradução , Ácido UrsólicoRESUMO
BACKGROUND/PURPOSE: In a recent study, we found that baicalin exhibited a potent analgesic effect on carrageenan-evoked thermal hyperalgesia. The underlining mechanisms may be associated with inhibition of inflammatory mediator overproduction, including proinflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). In the present study, we examined the effect of baicalin on the antinociceptive effect of morphine and histone deacetylase 1 (HDAC1) expression in the spinal cord dorsal horn in neuropathic pain rats. METHODS: Neuropathic pain was induced by tight ligation of the left L5 spinal nerve of the rats. An intrathecal catheter was implanted for drug administration. Nociception was assessed by using the plantar test with the Hargreaves radiant heat apparatus, and the von Frey test with the dynamic plantar anesthesiometer. Spinal cords were removed for histone acetyl-H3 and HDAC1 western blot analysis at the end of the nociceptive assessment. RESULTS: The results showed that hyperalgesia and allodynia were observed in the spinal nerve ligated (SNL) left hindlimb; it was companied by histone-H3 deacetylation and HDAC1 overexpression on the ipsilateral side of the spinal cord dorsal horn. Intrathecal injection of baicalin (10 µg) significantly attenuated the allodynia and hyperalgesia, and enhanced the antinociceptive effect of morphine (15 µg). Moreover, baicalin reversed the histone-H3 acetylation and suppressed HDAC1 expression on the ipsilateral side of the spinal cord dorsal horn of SNL rats. CONCLUSION: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.
Assuntos
Flavonoides/uso terapêutico , Histona Desacetilase 1/metabolismo , Hiperalgesia/tratamento farmacológico , Morfina/administração & dosagem , Neuralgia/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Acetilação , Animais , Histona Desacetilase 1/genética , Histonas/química , Injeções Espinhais , Ligadura , Masculino , Medição da Dor , Ratos , Ratos Wistar , Nervos Espinhais/lesõesRESUMO
STUDY OBJECTIVE: To define the depth of the thoracic epidural space in the paramedian axis. DESIGN: Retrospective study. SETTING: Operating room of a tertiary care medical center. PATIENTS: Nine hundred ninety-eight consecutive adults scheduled for elective major cardiothoracic/abdominal surgery and postoperative thoracic epidural pain control. INTERVENTIONS: The thoracic epidural pain control was accomplished via paramedian approach at indicated levels in 977 of 998 patients with uniform and well-standardized technique routinely performed in this institute. MEASUREMENTS: The depth of the epidural space, defined as the distance from the needle tip just penetrating the epidural layer to the overlying skin, was measured by directly checking the length markers displayed on the needle. Association between demographic variables and epidural depths at different thoracic levels was analyzed. MAIN RESULTS: The mean thoracic epidural depth was (mean+/-SD) 5.11+/-0.94 cm, which was positively correlated with the body weight (regression coefficient=0.039, P<.001) and body mass index but was unrelated to sex, age, or body height. On stepwise linear multivariate regression analysis, each 10 kg of increase in body weight would result in a 0.39-cm increase in the depth. Besides, this paramedian depth was 0.34 cm longer at upper thoracic levels (T9 and upper) than that at lower levels (T10 and lower, P<.001). CONCLUSIONS: Body weight, body mass index, and anatomical levels determine the paramedian thoracic epidural depth. The greater the patient's weight and the higher the puncture level, the deeper the thoracic epidural space from the body surface.