This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na ⁺-K ⁺-ATPase and Ca ²⁺-Mg ²⁺-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Animals ; Resveratrol ; Male ; Liver/pathology* ; Rats, Sprague-Dawley ; Rats ; Hindlimb Suspension ; Oxidative Stress/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Stilbenes/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis/drug effects*

This paper was designed to investigate the effect of laminar shear stress on matrix metalloproteinase -9 (MMP-9) expression in rat bone marrow-derived mesenchymal stem cells (MSCs), and the possible signal transduction mechanism involved. Rat bone marrow MSCs were isolated and cultured, then, exposed to laminar shear stress at indicated strengths such as low (5dyne/cm2), medium (15 dyne/cm2) and high (30 dyne/cm2) via parallel plate flow chamber. RT-PCR was used to analyze the expression of MMP-9. The signaling inhibitors such as Wortmannin (PI3K specific inhabitor), SB202190 (p38MAPK specific inhabitor), and PD98059 (ERK1/2 specific inhabitor) were used to investigate the possible mechanical signal transduction pathway. The results showed: (1) The expression of MMP-9 was weak in static state, however, MMP-9 expression increased when MSCs were exposed to 15 dyne/cm2 shear stress for 2 hours, and MMP-9 expression increased with the extension of stimulating time, and it reached the peak at 24 h; (2) MSCs were stimulated by shear stress for 2 hours at different strengths (5 dyne/cm2, 15 dyne/cm2, 30 dyne/cm2), and under all these conditions, the expression of MMP-9 increased, and reached the peak at 15 dyne/cm2; (3) After MSCs were pretreated by three kinds of signal pathway inhibitors, the expression of MMP-9 did not change obviously in Wortmannin group and PD98059 group, but it was significantly inhibited in SB202190 group. This study demonstrated that shear stress could induce the expression of MMP-9 in rat bone marrow-derived mesenchymal stem cells; the amount of MMP-9 expression was closely related to stimulating time and the strengths of shear stress; and p38MAPK signal pathway played a critical role during the process.
Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cells, Cultured ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Rats ; Signal Transduction ; Stress, Mechanical