Background: A major endogenous protective mechanism in many organs against ischemia/reperfusion (I/R) injury is ischemic preconditioning (IPC). By moderately uncoupling the mitochondrial respiratory chain and decreasing production of reactive oxygen species (ROS), IPC reduces apoptosis induced by I/R by reducing cytochrome c release from the mitochondria. One element believed to contribute to reduce ROS production is the uncoupling protein UCP2 (and UCP3 in the heart). Although its implication in IPC in the brain has been shown in vitro, no in vivo study of protein has shown its upregulation. Our first goal was to determine in rat hippocampus whether UCP2 protein upregulation was associated with IPC-induced protection and increased ROS production. The second goal was to determine whether the peptide ghrelin, which possesses anti-oxidant and protective properties, alters UCP2 mRNA levels in the same way as IPC during protection.

AIM:To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS:In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3ml/kg) containing Na 2 51 CrO 4 (0.5µ µ µ µ µCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol.RESULTS: Low does of P (1mg/kg, i.p.) enhanced the gastric emptying (75±3%, P<0.05) and high dose of P (5mg/kg, i.p.) inhibit it (42±11.2%, P<0.01). P (1mg/kg) increased the intestinal transit (4.2±0.3, P<0.05) while the higher dose (10-20mg/kg) had no effect. OT (0.8mg/kg, i.p.) inhibited the gastric emptying (23.5± 9.8%, P<0.01). The inhibitory effects of P(20mg/kg) (32±9.7%, P<0.05) and OT (0.8mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17±9.4%, P<0.01).CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.Liu CY, Chen LB, Liu PY, Xie DP, Wang PS. Effects of progesterone on gastric emptying and intestinal transit in male rats. World J Gastroenterol 2002;8(2):338-341

OT inhibits the motility of proximal colon in rabbits. The action is partly relevant with N receptor, but irrelevant with that of NO, progesterone or estrogen.

Survivin is an anti-apoptotic gene that decreases the apoptosis by depressing the expression of caspase-3. Hypoxia-inducible factor-1-alpha (HIF-1-alpha) is a transcription factor specifically activated by hypoxia. 2-methoxyestradiol (2ME2) is an estradiol derivative and a known HIF-1-alpha inhibitor. 2ME2 decreased apoptosis by inhibiting HIF-1-alpha. The aim of the present study was to investigate if survivin is involved in the anti-apoptotic effect of 2ME2. Male adult rats were used to make the global ischemia (GI) model. Ten minutes after GI, 2ME2 was injected intraperitoneally (16 mg/kg weight). Rats were killed at 6 hours, 12 hours, 24 hours, 48 hours, 96 hours, and 7 days. GI produced a marked increase in HIF-1-alpha expressions in the hippocampus at 6 hours and peaked at 48-96 hours. The expressions of survivin and caspase-3 were increased lightly in a similar time course. These molecular changes were accompanied by massive cell loss and apoptosis in the hippocampal regions. 2ME2 treatment reduced the expression of HIF-1-alpha, increased survivin expression, and decreased the expression of caspase-3. These results indicate that survivin and HIF-1-alpha were involved in the anti-apoptotic effect of 2ME2 treated following GI. 2ME2 may decrease the HIF-1-alpha expression, up-regulate the survivin expression, inhibit the expression of caspase-3, and finally reduce apoptosis after GI.

Hydroxysafflor yellow A (HSYA) is a main chemical component of the flower of Carthamus tinctorius. The present study investigated whether HSYA could attenuate brain injury induced by lymphostatic encephalopathy (LE). This was induced in adult male Wistar rats by cervical lymphatic blockade (CLB). Heart rate variability (HRV) was used as an indirect measurement of the regulatory function of the autonomic nervous system by recording the ECG signals from rats. It was shown that treatment with HSYA (5 mg/kg, i.p.) significantly alleviated the neurological deficits observed in rats with LE. Histological staining revealed that HSYA treatment attenuated LE-induced cell apoptosis in the rostral ventrolateral medullus (RVLM). Animals in the LE groups exhibited impaired regulatory roles of the autonomic nervous system in cardiovascular function, which was suppressed by pretreatment with HSYA. Additionally, HSYA administration significantly prevented the decrease of endothelial nitric oxide synthase (eNOS) mRNA and protein expression in the RVLM of rats with LE. These findings suggest that HSYA might provide neuroprotection against LE-induced brain injury and the associated functional alterations, which is likely regulated by the nitric oxide pathway.