[Optimal conditions of bone marrow mesenchymal stem cells on paraquat-induced acute lung injury in rats].

OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on acute lung injury induced by paraquat (PQ) poisoning in rats, and to identify the optimal transplantation conditions. METHODS: Two hundred female rats were randomly divided into six groups, i.e., PQ group (n = 15), BMSC treatment group 1 (n = 15 for each subgroup), BMSC treatment group 2 (n = 15 for each subgroup), BMSC control group 1 (n = 15 for each subgroup), BMSC control group 2 (n = 15), and normal control group (n = 5). In the PQ group, each rat was intraperitoneally injected with 20% PQ solution (15 mg/kg). In BMSC treatment group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7)or 10(8) BMSCs (1 ml) after 6 hours of PQ exposure. In BMSC treatment group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml) after 1, 6, 12, or 24 hours of PQ exposure. In BMSC control group 1, each rat was injected via the caudal vein with 1×10(5), 10(6), 10(7), or 10(8) BMSCs (1 ml). In BMSC control group 2, each rat was injected via the caudal vein with 1×10(7) BMSCs (1 ml). In the normal control group, each rat was intraperitoneally injected with an equal volume of 0.9% saline. The lung wet/dry weight ratio and plasma tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels were measured at 1, 3, and 7 days after various treatments. RESULTS: Compared with the normal control group, the PQ group showed significantly higher lung wet/dry weight ratios at 3 and 7 days after PQ exposure and significantly higher plasma TNF-α and MDA levels at 1, 3, and 7 days after PQ exposure (P < 0.01). Compared with the PQ group, BMSC treatment group 1 showed significantly lower lung wet/dry weight ratios at 7 days after injection of 1×10(6) and 10(7) BMSCs, significantly lower plasma TNF-α levels at 3 and 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs, and significantly lower plasma MDA levels at 3 days after injection of 1×10(6) and 10(7) BMSCs and at 7 days after injection of 1×10(5), 10(6), and 10(7) BMSCs (P < 0.05 or P < 0.01). Compared with the PQ group, BMSC treatment group 2 showed significantly lower lung wet/dry weight ratios at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, significantly lower plasma TNF-α levels at 3 and 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure, and significantly lower plasma MDA levels at 3 days after injection of BMSCs following 6 hours of PQ exposure and at 7 days after injection of BMSCs following 1, 6, and 12 hours of PQ exposure (P < 0.01). CONCLUSION: BMSCs have a protective effect on the lung in rats with PQ poisoning, and the effect is closely related to the transplantation time and number of transplanted BMSCs. After 6 hours of PQ exposure, intravenous injection of 1×10(7) BMSCs can result in significant decreases in lung wet/dry weight ratio and plasma TNF-α and MDA levels.

Suppressive effects of intrathecal paeoniflorin on bee venom-induced pain-related behaviors and spinal neuronal activation.

Recently, paeoniflorin (PF) administered systemically was found to have analgesic effects against inflammatory pain and hypersensitivity in a naloxone-reversible manner. In the present study, we adopted intrathecal administration to evaluate whether PF has direct antinociceptive actions at the spinal level. Pain-related behaviors and spinal c-Fos expression were induced by subcutaneous injection of bee venom (BV) into one hind paw of a rat. Intrathecal pretreatment of PF resulted in an inhibition of the BV-induced persistent spontaneous nociception and partially suppressed the occurrence of both thermal and mechanical hypersensitivity. Moreover, the PF-produced antinociception was completely reversed by naloxone. We further evaluated the intrathecal effects of the drug on the BV-induced c-Fos expression. The result showed that intrathecal PF preconditioning was effective to suppress spinal c-Fos expression in both superficial (lamina I-II) and deep (lamina IV-VI) layers of the L(4-5) dorsal spine. This result showed that PF has a direct pharmacological action in the spinal cord dorsal horn via activation of opioid receptors.

Region- or state-related differences in expression and activation of extracellular signal-regulated kinases (ERKs) in naïve and pain-experiencing rats.

BACKGROUND: Extracellular signal-regulated kinase (ERK), one member of the mitogen-activated protein kinase (MAPK) family, has been suggested to regulate a diverse array of cellular functions, including cell growth, differentiation, survival, as well as neuronal plasticity. Recent evidence indicates a role for ERKs in nociceptive processing in both dorsal root ganglion and spinal cord. However, little literature has been reported to examine the differential distribution and activation of ERK isoforms, ERK1 and ERK2, at different levels of pain-related pathways under both normal and pain states. In the present study, quantitative blot immunolabeling technique was used to determine the spatial and temporal expression of ERK1 and ERK2, as well as their activated forms, in the spinal cord, primary somatosensory cortex (SI area of cortex), and hippocampus under normal, transient pain and persistent pain states. RESULTS: In naïve rats, we detected regional differences in total expression of ERK1 and ERK2 across different areas. In the spinal cord, ERK1 was expressed more abundantly than ERK2, while in the SI area of cortex and hippocampus, there was a larger amount of ERK2 than ERK1. Moreover, phosphorylated ERK2 (pERK2), not phosphorylated ERK1 (pERK1), was normally expressed with a high level in the SI area and hippocampus, but both pERK1 and pERK2 were barely detectable in normal spinal cord. Intraplantar saline or bee venom injection, mimicking transient or persistent pain respectively, can equally initiate an intense and long-lasting activation of ERKs in all three areas examined. However, isoform-dependent differences existed among these areas, that is, pERK2 exhibited stronger response than pERK1 in the spinal cord, whereas ERK1 was more remarkably activated than ERK2 in the S1 area and hippocampus. CONCLUSION: Taken these results together, we conclude that: (1) under normal state, while ERK immunoreactivity is broadly distributed in the rat central nervous system in general, the relative abundance of ERK1 and ERK2 differs greatly among specific regions; (2) under pain state, either ERK1 or ERK2 can be effectively phosphorylated with a long-term duration by both transient and persistent pain, but their response patterns differ from each other across distinct regions; (3) The long-lasting ERKs activation induced by bee venom injection is highly correlated with our previous behavioral, electrophysiological, morphological and pharmacological observations, lending further support to the functional importance of ERKs-mediated signaling pathways in the processing of negative consequences of pain associated with sensory, emotional and cognitive dimensions.

Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity.

Paeoniflorin (PF), one of the active chemical compounds identified from the root of Paeonia lactiflora Pall, has been well-established to exhibit various neuroprotective actions in the central nervous system (CNS) after long-term daily administration. In the present study, by using the bee venom (BV) model of nociception and hypersensitivity, antinociceptive effects of PF were evaluated by intraperitoneal administration in conscious rats. When compared with saline control, systemic pre- and post-treatment with PF resulted in an apparent antinociception against both persistent spontaneous nociception and primary heat hypersensitivity, while for the primary mechanical hypersensitivity only pre-treatment was effective. Moreover, pre- and early post-treatment with PF (5 min after BV injection) could successfully suppress the occurrence and maintenance of the mirror-image heat hypersensitivity, whereas late post-treatment (3 h after BV) did not exert any significant impact. In the Rota-Rod treadmill test, PF administration did not affect the motor coordinating performance of rats. Furthermore, systemic PF application produced no significant influence upon BV-induced paw edema and swelling. Finally, the PF-produced antinociception was likely to be mediated by endogenous opioid receptors because of its naloxone-reversibility. Taken together, these results provide a new line of evidence showing that PF, besides its well-established neuroprotective actions in the CNS, is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity via opioid receptor mediation.

Serum adropin levels are decreased in patients with acute myocardial infarction.

OBJECTIVE: Adropin is a recently identified bioactive protein that is important for energy homeostasis and maintaining insulin sensitivity. We sought to detect serum adropin levels in acute myocardial infarction (AMI) patients. METHODS: We enrolled 138 AMI patients, 114 stable angina pectoris (SAP) patients and 75 controls. Adropin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum adropin levels were significantly lower in patients with AMI compared with SAP patients or controls (P<0.01). Multivariate logistic regression demonstrated that lower adropin was the independent predictor for the presence of AMI in coronary artery disease (CAD) patients (P<0.01). Serum adropin levels were negatively associated with body mass index (BMI) (P<0.01) and triglyceride levels (P<0.05) in AMI patients. CONCLUSION: Decreased serum adropin levels are associated with the presence of AMI in CAD patients. These results revealed that adropin might represent as a novel biomarker for predicting AMI onset in CAD patients.