Chondroprotective effects of Apolipoprotein D in knee osteoarthritis mice through the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Because the pathophysiology of osteoarthritis (OA) has not been fully elucidated, targeted treatments are lacking. In this study, we assessed the role and underlying mechanism apolipoprotein D (APOD) on the development of OA. METHODS: To establish an in vitro OA model, we extracted primary chondrocytes from the cartilage of C57BL/6 mice and stimulated the chondrocytes with IL-1ß. After APOD intervention or incubation with an overexpressing plasmid, we detected inflammatory-related markers using RT-qPCR, Western blotting, and ELISA. To detect apoptosis and autophagy-related markers, we used flow cytometry, immunofluorescence, and transmission electron microscopy (TEM). Finally, we measured the level of oxidative stress. We also used RNA-seq to identify the APOD-regulated downstream signaling pathways. We used an in vivo mice OA model of the anterior cruciate ligament transection (ACLT) and administered intra-articular adenovirus overexpressing APOD. To examine cartilage damage severity, we used immunohistochemical analysis (IHC), micro-CT, scanning electron microscopy (SEM), and Safranin O-fast green staining. RESULTS: Our results showed that APOD inhibited chondrocyte inflammation, degeneration, and apoptosis induced by IL-1ß. Additionally, APOD reversed autophagy inhibition and oxidative stress and also blocked activation of the PI3K/AKT/mTOR signaling pathway induced by IL-1ß. Finally, overexpression of the APOD gene through adenovirus was sufficient to mitigate OA progression. CONCLUSIONS: Our findings revealed that APOD had a chondroprotective role in OA progression by the PI3K/AKT/mTOR signaling pathway.

Effects of stellate ganglion block on the peri-operative vasomotor cytokine content and intrapulmonary shunt in patients with esophagus cancer.

OBJECTIVE: To investigate the effects of stellate ganglion block (SGB) on the peri-operative vasomotor cytokine content and intrapulmonary shunt in patients with esophagus cancer who underwent thoracotomy. MATERIALS AND METHODS: Forty patients undergoing elective resection of esophageal cancer patients who had I~II American Society of Anesthesiologist (ASA) were randomly divided into total intravenous anesthesia group (group N, n=20) and total intravenous anesthesia combined with SGB group (group S, n=20, 0.12 mL/kg 1% lidocaine was used for SGB 10 min before induction). Heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP) and continuous cardiac output (CCO) were continuously monitored. The blood from internal jugular vein was drawn respectively before induction (T0), and 30 min (T1), 60 min (T2) and 120 min (T3) after one-lung ventilation (OLV), and 30 min (T4) after two-lung ventilation. The contents of plasma endothelin (ET), nitric oxide (NO) and calcitonin gene-related peptide (CGRP) were detected with enzyme linked immunosorbent assay (ELISA). Meanwhile, arterial and mixed venous blood samples were collected for determination of blood gas and calculation of intrapulmonary shunt fraction (Qs/Qt). RESULTS: During OLV, ET contents were increased significantly in two groups (P<0.05), and no significant difference was presented (P>0.05). NO content in group S was obviously higher than in group N at T3 (P<0.05), whereas CGRP content in group N was markedly lower than in group S at each time point (P<0.05). Qs/Qt was significantly increased in both groups after OLV, but there was no statistical significant regarding the Qs/Qt at each time point between two groups. CONCLUSIONS: Total intravenous anesthesia combined with SGB is conducive to regulation of perioperative vasomotor cytokines in thoracotomy, and has little effect on intrapulmonary shunt at the time of OLV.