[Abstract ] Objective The purpose of this study was to observe the effects of dl-3n-butylphthalide (NBP) sodium chloride injection post-processing on the expressions of X-inhibitor of apoptosis (XIAP) and Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in the hippocampus CA1 neurons of focal cerebral ischemia reperfusion (IR) rats, and to investigate the brain-protection mechanisms of NBP. Methods A total of65 adult male Sprague-Dawley rats were divided into five groups of equal number, sham op-eration, IR, and low-,medium -and high-dose NBP, according to the random number table. The IR models were established by modified ligation of the middle cerebral artery.The animals in the NBP groups received intra-abdominal injection of NBP at 2, 4, and 6 mg/kg, re-spectively.All the rats were sacrificed at 24 hours after modeling,neurological scores obtained by Zea Longa, the volume of infarction measured by TTC staining, the number of apoptotic cells counted by TUNEL, and the expressions of XIAP and BNIP3 detected by immunohistochemistry and real-time PCR. Results The neural function defect scores were markedly lower in low-, medium-and high-dose NBP groups than in IR model rats (P<0.05), with statis-tically significant differences among the three dose groups (P<0.05).The volume of infarction was remarkably higher in the low-dose than in the medium-and high-dose NBP groups (P<0.05).The number of apoptotic cells in the hippocampus CA1 neurons was de-creased in the NBP groups as compared with the IR models (P<0.05).The XIAP-and BNIP3-positive cells were significantly in-creased in the IR model rats as compared with the sham operation group ([22.31 ±0.94] and [60.13 ±2.59]/HP vs [3.07 ±1.43] and [5.78 ±0.44]/HP, P<0.05).In comparison with the IR models, the NBP-treated rats showed a progressively increased number of XIAP-positive cells in low-, medium-, and high-dose groups ([28.70 ±1.18], [32.79 ±0.88], and [37.01 ±1.24]/HP) (P<0.05) but a decreased number of BNIP3-positive cells in the three dose groups ([52.07 ±1.02], [40.30 ±2.00], and [31.04 ± 0.43]/HP) (P<0.05).Similarly, the expression of XIAP mRNA was up-regulated while that of BNIP3 mRNA down-regulated in the NBP treatment groups as compared with the IR model rats, both in a dose-dependent manner (P<0.05). Conclusion NBP post-processing has a neuroprotective effect on IR rats, which is associated with its impact on the expressions of XIAP and BNIP3.

Aim To study the effect of genistein on contractility of isolated papillary muscles in guinea pig and its mechanisms.Methods Isolated guinea pig papillary muscles were suspended in organ baths containing KH solution,and the effect of genistein on contractility of myocardium was observed after an equilibration period.Results Genistein and isoprenaline hydrochloride showed positive inotropic effects on contractility of myocardium in a dose-dependent manner(1～100 ?mol?L~(-1)) Propranolol(1 ?mol?L~(-1)) and verapamil hydrochloride(0.5 ?mol?L~(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride(2 ?mol?L~(-1)),but did not change the effect of genistein(100 ?mol?L~(-1)).Furthermore,the enhancement of the contractility induced by elevation of extracellular Ca~(2+) concentration in papillary muscles did not show any change after pretreatment with genistein(1,10 ?mol?L~(-1)).Finally,the positive inotropic effect of genistein was attenuated partially by tamoxifen(1 ?mol?L~(-1)),however,was not influenced by sodium orthovanadate(1 ?mol?L~(-1)).Conclusions Genistein has the positive inotropic effect on guinea pig papillary muscles,which is not related to the activation of Ca~(2+) channel on cell membrane,? adrenoceptor and tyrosine kinase pathway,but this effect may involve in uptake and utilization of sarcoplasmic reticulum Ca~(2+).

OBJECTIVE To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway. METHODS The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia- inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot. RESULTS Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜ 0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）. CONCLUSIONS Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.