ABSTRACT
OBJECTIVE: Intervertebral disc degeneration (IVDD) is associated with the apoptosis of nucleus pulposus (NP) cells. Previous studies have shown that PTEN plays crucial roles in cell survival and apoptosis. The effect of PTEN inhibitors on cell survival following IVDD has been rarely examined. In this study, we investigated the protective effect of SF1670, as a specific PTEN inhibitor, on an in vitro NP cells degenerated model. PATIENTS AND METHODS: We collected human disc samples from IVDD patients and detected PTEN expression in them with different degenerated degrees. NP cells were isolated from the samples and exposed to IL-1ß with or without SF1670. Then, cells viability was determined by CCK-8 assay. We also measured the levels of collagen II, p16, p53, PTEN, Akt, aggrecan, caspase 3/9, Bax, Bcl-2, and several inflammatory factors in NP cells. RESULTS: We found that the expression of PTEN markedly increased in severely degenerated disc tissues. The data showed that IL-1ß upregulated the expressions of p16, p53, PTEN, caspase 3/9, and Bax, but decreased the expressions of collagen II, Akt, aggrecan, and Bcl-2. Surprisingly, the treatment with SF1670 could significantly reverse the regulatory effects of IL-1ß. Moreover, relative levels of IL-6, IL-8, TNF-α, and MMP3/9/13 were significantly suppressed by SF1670 stimuli compared with IL-1ß group. CONCLUSIONS: Overall, these results demonstrated that SF1670 prevented NP degradation via suppressing apoptosis and inflammation through inhibition of PTEN and activation of Akt. SF1670 may become a novel target for the therapy of IVDD in the future.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Nucleus Pulposus/cytology , PTEN Phosphohydrolase/antagonists & inhibitors , Phenanthrenes/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Adult , Aged , Aggrecans/genetics , Anti-Inflammatory Agents/therapeutic use , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Collagen Type II/genetics , Cytokines/genetics , Female , Humans , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/metabolism , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 3/genetics , Middle Aged , Nucleus Pulposus/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/drug effectsABSTRACT
OBJECTIVES: The objective of this study was to explore the effect of various bile duct flush (BDF) solutions on biliary tract preservation of donated livers in rats. METHODS: We studied the effects of BDF solutions and cold ischemic times on biliary tract preservation, using 2 kinds of solutions: (1) BDFa with normal saline (NS), or hypertonic citrate-adenine kidney preservation in vivo (HCA), and (2) BDFb with University of Wisconsin solution (UW), or histidine-tryptophan-ketoglutarate solution (HTK). The cold ischemic times (CIT) were 4, 8, or 12 hours. Forty-five healthy male Wistar rats were randomly divided into 9 groups of 5 rats each using a [L(9)(3(4))] orthogonal table. Biliary tract tissues were examined at the corresponding cold preservation times for the following: microscopic changes in bile duct cells; TUNEL (Transferase-mediated, dUTP-bitin nick end labeling) procedure assays apoptotic indices (AI) of endothelial cells in the biliary tract; ultrastructural changes; and average volumes (V) and density (Nd) of mitochondria in endothelial cells calculated using an image analysis system. The results were evaluated by analysis of variance (ANOVA) and direct analysis by an orthogonal design. RESULTS: AI of biliary tract endothelial cells showed significance (P < .01) of cold preservation of the biliary tract of donor liver with BDFa or BDFb and CIT; furthermore, HCA, HTK, and 4-hour CIT were all ideal. V and Nd of mitochondrial endothelial cells were significantly increased (P < .01) with BDFa, BDFb, and CIT; furthermore, factors HCA, HTK, and 4-hour CIT were all ideal. CONCLUSIONS: Cold preservation injuries to the biliary tract of a donor liver may be greatly decreased by efficient and sufficient flushing of the bile tract. A suitable bile duct solution greatly decreases cold preservation injuries and protects endothelial cells.
Subject(s)
Bile Ducts/physiology , Biliary Tract/physiology , Liver Transplantation/physiology , Liver/physiology , Organ Preservation Solutions , Organ Preservation/methods , Animals , Apoptosis , Bile/physiology , Biliary Tract/cytology , Biliary Tract/pathology , Epithelial Cells/cytology , Epithelial Cells/physiology , Humans , In Situ Nick-End Labeling , Liver Transplantation/methods , Male , Rats , Tissue DonorsABSTRACT
Borneol is an organic drug having property to form eutectic mixture with salicylic acid. We compared the transdermal absorption rate of borneol alone with that of borneol-salicylic acid eutectic mixture in hairless rats. The results showed that the borneol-salicylic acid eutectic mixture can evidently increase the absorption rate of borneol and provided a method for manufacturing borneol preparation which can easily be absorbed transdermally.
