Analysis Of Urinary Proteomics Of Osteoarthritis And Analysis Of Blood Inflammation Level After Non - Steroidal Anti - Inflammatory Drugs

ObjectivePart one:To identify differentially expressed proteins from the urine of women with and without osteoarthritis and to explore the potential pathogenesis of osteoarthritis.Part two:Pain after total knee arthroplasty (TKA) and total hip arthroplasty (THA) is severe. Non-steroid anti-inflammatory drugs (NSAIDs) are recommended for postoperative pain management. We evaluated the effect of perioperative administration of parecoxib sodium (PS) on postoperative pain, analgesic use, recovery of function, inflammatory response, and bleeding risk after TKA and THA.MethodsPart one:Urine samples were collected from two groups of age-and gender-matched patients with and without osteoarthritis. These samples were subjected to isobaric tags for relative and absolute quantitation analysis to identify the proteins involved in osteoarthritis. Signaling pathways were analyzed using the Metacore software, and the identified proteins were validated by western blotting.Part two:76 patients who underwent TKA and 74 patients underwent THA were enrolled in this prospective, randomized, patient-and observer-blinded control study. In each group, patients were randomized into the study group and control group. The PS group received a single 40-mg dose of PS 30 min before incision,9 pm on the day of surgery, and every 12 h for 2 days, along with patient-controlled intravenous analgesia. The control group received saline injection at the same time point. Pain was assessed at rest and during movement using a visual analog scale (VAS). Morphine consumption and joint function were recorded. As indicators of the inflammatory response, body temperature, leukocyte count, levels of high-sensitivity C-reactive protein level, and serum levels of interleukin IL-6 and IL-10 were measured. Perioperative blood loss, blood drainage, and blood transfusion were documented.ResultsPart one:A total of 1,413 proteins were identified by using iTRAQ. technology.394 proteins were differentially expressed in osteoarthritis patients compared with the control group; 224 of these proteins were significantly downregulated and 170 were significantly up-regulated in women with osteoarthritis. Western blotting was used to validate the relative increases in serum protein levels for four of the identified proteins.Part two:In patients underwent TKA, VAS both at rest and during movement were improved significantly in the parecoxib group, compared with the control group at most of the observation points in the first four days after the surgery. The morphine consumption were significantly reduced in the parecoxib group (24.0±12.5mg vs. 38.6±16.5mg, p=0.022) while the PCIA duration of the parecoxib group were significantly shorter than the control group (49.0±11.4h vs.57.6±15.0h, p=0.037). The active range of motion (ROM) on postoperative day 3 and day 6 were also significantly improved in the parecoxib group (68.2±8.5°vs.60.4±10.7°, p=0.04 and 80.0±9.4° vs. 70.7±10.5°, p=0.04). The body temperature and leukocyte count on POD1 and POD3, the hs-CRP on POD3 and POD6 were also significantly decreased in the parecoxib group. There was no significant difference between the two groups in perioperative blood loss, drainage and blood transfusion rate. In patients underwent THA, VAS at rest were improved significantly in the parecoxib group, compared with the control group at 12h and 24h. VAS at movement were improved significantly at 12h,24h,36h, 48h, POD3 and POD4. The morphine consumption were significantly reduced in the parecoxib group (13.6mg±6.3mg vs.31.2mg ± 15.7mg, P=0.002) while the withdrawal of PCIA were significantly earlier (11.8h±4.4h vs.35.3h±15.4h). The body temperature was significantly decreased in the parecoxib group on POD1 and POD3. There was no significant difference between the two groups in perioperative blood loss, drainage and blood transfusion rate.ConclusionPart one:The differentially expressed proteins identified in our study are mainly involved in cell adhesion, the immune response, and the inflammatory response. On the basis of the results of this study, it can be concluded that these mechanisms may play an important role in the pathogenesis of osteoarthritis. Additionally, these proteins may provide clues for not only a promising biomarker for the diagnosis of osteoarthritis but also a potential target for therapeutic intervention.Part two:Perioperative administration of PS combined with opioids is an effective and safe regimen for pain management after TKA and THA.