RESUMO
Objective: To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells. Methods: Human liver L02 oxidative injury model was established with 0.1 mmol/ L H(2)O(2) intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H(2)O(2), H(2)O(2) + JDHY (0.5 mg/ml), H(2)O(2) + JDHY (1 mg/ml), and H(2)O(2) + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results: Compared with the normal group, the cell proliferation activity (P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H(2)O(2) group were all significantly reduced (P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased (P < 0.05). Compared with H(2)O(2) group, the cell proliferation activity (P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H(2)O(2) + JDHY (1 mg/ml) and H(2)O(2) + JDHY (1.5 mg/ml) group (P < 0.05) were all significantly increased (P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased (P < 0.05). Conclusion: Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.
Assuntos
Peróxido de Hidrogênio , Fosfatidilinositol 3-Quinases , Animais , Apoptose , Hepatócitos/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo , CoelhosRESUMO
The incidence of persistent pain after cesarean deliveries (CD) varies but is much lower than after comparable surgeries. However, with over four million deliveries annually and a rising CD rate, even a low prevalence of persistent pain after CD impacts many otherwise healthy young women. Consideration of the pathophysiology of persistent pain after surgery and the risk factors predisposing women to persistent and chronic pain after CD provides insights into the prevention and treatment of persistent pain; and improves the quality of care and recovery after CD. The findings that the peripartum state and oxytocin confer protection against persistent pain may provide new and interesting perspectives for the prevention and treatment of chronic pain caused by trauma or surgery. Predictive tools available to identify and target patients at high risk of acute and chronic pain have mostly weak to modest predictive correlations and many are either not clinically feasible or too time-consuming to apply. Persistent pain has been linked to the severity of acute postoperative pain and opioid exposure. Modified surgical techniques, neuraxial anesthesia and opioid-sparing analgesia may help limit the development of persistent and chronic pain. The goal of this narrative review is to examine the incidence of persistent pain after CD; review briefly the underlying pathophysiology of persistent pain and the transition from acute to chronic pain (with particular emphasis on the uniqueness after CD); and to review modifiable risk factors and prevention strategies that identify at-risk patients and allow tailored treatment.
Assuntos
Cesárea , Dor Crônica/fisiopatologia , Dor Pós-Operatória/fisiopatologia , Adulto , Dor Crônica/terapia , Feminino , Humanos , Dor Pós-Operatória/terapia , GravidezRESUMO
DNA polymerase beta functions in both base excision repair and meiosis. Errors committed by polymerase beta during these processes could result in mutations. Using a complementation system, in which rat DNA polymerase beta substitutes for DNA polymerase I of Escherichia coli, we previously isolated a DNA polymerase beta mutant in which Tyr-265 was altered to Cys (Y265C). The Y265C mutant is dominant to wild-type DNA polymerase beta and possesses an intrinsic mutator activity. We now have expressed the wild-type DNA polymerase and the Y265C mutator mutant in mouse LN12 cells, which have endogenous DNA polymerase beta activity. We demonstrate that expression of the Y265C mutator mutant in the LN12 cells results in an 8-fold increase in the spontaneous mutation frequency of lambdacII mutants compared with expression of the wild-type protein. Expression of Y265C results in at least a 40-fold increase in the frequency of deletions of three bases or more and a 7-fold increase in point mutations. Our results suggest that the mutations we observe in vivo result directly from the action of the mutator polymerase. To our knowledge, this is the first demonstration of a mutator phenotype resulting from expression of a DNA polymerase mutator mutant in mammalian cells. This work raises the possibility that variant polymerases may act in a dominant fashion in human cells, leading to genetic instability and carcinogenesis.