Adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin signaling participates in the protective effect of chronic intermittent hypobaric hypoxia on vascular endothelium of metabolic syndrome rats.

Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) protects vascular endothelium function through ameliorating autophagy in mesenteric arteries of metabolic syndrome (MS) rats. This study aimed to investigate the role of adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling in CIHH effect. Six-week-old male Sprague-Dawley rats were divided into control (CON), MS model, CIHH treatment (CIHH), and MS + CIHH groups. Serum pro-inflammatory cytokines were measured. The endothelium dependent relaxation (EDR), endothelial ultrastructure and autophagosomes were observed in mesenteric arteries. The expression of phosphor (p)-AMPKα, p-mTOR, autophagy-related and endoplasmic reticulum stress-related proteins, p-endothelial nitric oxide synthase, and cathepsin D were assayed. In MS rats, pro-inflammatory cytokines were increased, EDR was attenuated, and endothelial integrity was impaired. In addition, the expression level of p-AMPKα and cathepsin D was down-regulated, but the level of p-mTOR was up-regulated. While in MS + CIHH rats, all aforementioned abnormalities were ameliorated, and the beneficial effect of CIHH was cancelled by AMPKα inhibitor. In conclusion, AMPK-mTOR signaling pathway participates in the protection of CIHH on vascular endothelium of MS rats.

Chronic intermittent hypobaric hypoxia provides vascular protection in the aorta of the 2-kidney, 1-clip rat model of hypertension.

Many studies have demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can reduce blood pressure in spontaneously hypertensive rats and renovascular hypertensive (RVH) rats in which endothelial dysfunction is determined as a critical factor. However, whether CIHH can regulate vasodilation of the aorta in RVH rats remains unknown. The purpose of this study was to investigate the effect of CIHH on impaired relaxation of the aorta in the 2-kidney, 1-clip (2K1C) RVH rat model. The results showed CIHH improved the impaired endothelium-dependent relaxation in the 2K1C rat aorta. The endothelial dysfunction was prevented by the p38 antagonist SB203580, but not by the ERK1/2 antagonist PD98059 or JNK antagonist SP600125. Furthermore, the expression of p-eNOS, HIF-1α, and HIF-2α increased while that of p-p38 and BMP-4 decreased in CIHH-treated aortas from 2K1C rats. Finally, the p-eNOS expression was upregulated and the p-p38 expression was downregulated by pre-incubation of SB203580 or the BMP-4 antagonist Noggin with the aorta. CIHH ameliorated the impairment of endothelium-dependent relaxation through upregulating the expression of p-eNOS, which may be mediated by the inhibition of BMP-4/p-p38 MAPK, and upregulating the expression of HIFs in the 2K1C rat aorta.

Enhanced vasorelaxation effect of endogenous anandamide on thoracic aorta in renal vascular hypertension rats.

Emerging evidence has indicated that anandamide (AEA) is able to stimulate vasorelaxation in both spontaneously hypertensive rats (SHRs) and L-NAME-induced hypertensive rats. Yet it remains unknown whether AEA modulates vasomotion of the aorta in renovascular hypertensive (RVH) rats. The aim of present study is to explore the effect of AEA on the relaxation of thoracic aortas in two-kidney one-clip (2K1C)-induced RVH rats. It is demonstrated that AEA stimulates a pronounced relaxation in the aortas of 2K1C rats compared with sham rats. The enhanced relaxation caused by AEA in aortas from 2K1C rats was diminished in the presence of the cannabinoid receptor-1 (CB1 ) antagonist AM251 and the CB2 receptor antagonist AM630. Likewise, the vasodilation action of AEA was blocked in L-NAME-treated or endothelium-denuded aortas. The Western blot results revealed that the expression of CB1 and CB2 receptors was increased in the 2K1C rat aortas compared with sham rats. The phosphorylation of endothelial nitric oxide synthase (p-eNOS) at the activation site Ser1177 was enhanced in AEA-treated rings from 2K1C rats in both time-dependent and dose-dependent manners. The augmented p-eNOS expression was inhibited by the co-treatment with AM251 or AM630. Taken together, the present study demonstrated that AEA enhanced endothelium-dependent aortic relaxation through activation of both CB1 and CB2 receptors and P-eNOS/NO pathway in 2K1C rats.

Opioid receptors mediate enhancement of ACh-induced aorta relaxation by chronic intermittent hypobaric hypoxia.

The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P < 0.05). (2) This enhancement of ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P < 0.05). (3) The expressions of δ, µ and κ opioid receptors in thoracic aorta of CIHH rats were up-regulated compared with those in control rats (P < 0.05). (4) The enhancement of CIHH on relaxation of thoracic aorta was reversed by glibenclamide, an ATP-sensitive potassium channel (KATP) blocker (P < 0.05). The results suggest that opioid receptors are involved in CIHH-enhanced ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.

Low sodium intake ameliorates hypertension and left ventricular hypertrophy in mice with primary aldosteronism.

The goal of this paper is to elucidate the effects of sodium restriction on hypertension and left ventricular (LV) hypertrophy in a mouse model with primary aldosteronism (PA). Mice with genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels (TASK-/-) were used as the animal model of PA. Parameters of the LV were assessed using echocardiography and histomorphology analysis. Untargeted metabolomics analysis was conducted to reveal the mechanisms underlying the hypertrophic changes in the TASK-/- mice. The TASK-/- adult male mice exhibited the hallmarks of PA, including hypertension, hyperaldosteronism, hypernatremia, hypokalemia, and mild acid-base balance disorders. Two weeks of low sodium intake significantly reduced the 24-h average systolic and diastolic BP in TASK-/- but not TASK+/+ mice. In addition, TASK-/- mice showed increasing LV hypertrophy with age, and 2 weeks of the low-sodium diet significantly reversed the increased BP and LV wall thickness in adult TASK-/- mice. Furthermore, a low-sodium diet beginning at 4 weeks of age protected TASK-/- mice from LV hypertrophy at 8-12 weeks of age. Untargeted metabolomics demonstrated that the disturbances in heart metabolism in the TASK-/- mice (e.g., Glutathione metabolism; biosynthesis of unsaturated fatty acids; amino sugar and nucleotide sugar metabolism; pantothenate and CoA biosynthesis; D-glutamine and D-glutamate metabolism), some of which were reversed after sodium restriction, might be involved in the development of LV hypertrophy. In conclusion, adult male TASK-/- mice exhibit spontaneous hypertension and LV hypertrophy, which are ameliorated by a low-sodium intake.

[Cluster analysis on authorized patents of compound traditional Chinese medicines with different efficacy in 2010].

OBJECTIVE: To discuss the authorized patent of compound traditional Chinese medicines with different efficacy in 2010, in order to provide reference for R&D of relevant compounds and patent protection. METHOD: Literatures for patents of compound traditional Chinese medicines were searched to screen relevant data and create a sample space. The samples were classified by hierarchical cluster procedures and iterative partitioning procedures using "authorized percentage" and "authorized time interval" as variable quantities. The comprehensive results generated by the two clustering methods were used to draw a conclusion. RESULT: The samples were classified into four groups by clustering methods, each has significant difference in authorized patents' number and authorized time interval with others. CONCLUSION: Among compounds showing therapeutic advantage of traditional Chinese medicines, patents with short authorization period and in less number can be given most attention for patent application. Those with longer authorization period and in less number can be given more attention. While those with shorter authorization period and in large number can also be given attention for information guidance for traditional Chinese medicine science and technology and commercialization of patent achievements.

[Analyses on positive influence of harmonous development of traditional Chinese medicine compounds' researchs and patent protection].

Current patent protection of traditional Chinese medicine (TCM) compounds is far from being satisfactory with increasing research and development achievements. As patent protection of traditional Chinese medicine compounds is closely related with many fields such as research and development of new TCM drugs, industrial development and TCM internationalization, the development of research and harmonious development of TCM compounds and their patent protection is bound to have a far-reaching influence on domestic and even international societies.

[Effects of exogenous hydrogen sulfide on pulmonary hypertension in rabbits with endotoxic shock].

Objective: To investigate the effects of exogenous hydrogen sulfide (H2S) on pulmonary vascular reactivity induced by endotoxic shock (ES) in rabbits. Methods: In this experiment, the model of endotoxic shock (ES) was induced by injection of lipopolysaccharides (LPS) to New Zealand big eared white rabbit through jugular vein (8 mg/0.8 ml/kg), the intervention was performed by H2S donor(sodium hydrosulfide, NaHS) which was injected intraperitoneally (28 µmol/kg) 15 min in advance. New Zealand rabbits were randomly divided into 4 groups(n=8):control group, LPS group, LPS+NaHS group and NaHS group. The changes of mean arterial pressure (MAP) and mean pulmonary arterial pressure (MPAP) were detected. The tension of pulmonary artery ring (PARs) was detected byin vitro vascular ring technique. The ultrastructure of pulmonary artery wall and pulmonary artery endothelial cells were observed by light microscope and scanning electron microscope. Results: ①MAP was decreased while MPAP was increased in rabbits after LPS injection, and ES animal model was established successfully. Compared with LPS group, mPAP of rabbit in LPS+NaHS group was decreased significantly (all P＜0.05). ②Compared with normal control group, pulmonary artery of rabbits in LPS group had an increased contractile response to phenylephrine (PE) and a decreased relaxation response to acetylcholine (ACh) (both P＜0.01); Compared with LPS group, pulmonary artery of rabbits in LPS+NaHS group had a decreased contractile response to PE and an increased relaxation response to ACh (both P＜0.05). ③Under light microscope, the structure of vascular endothelial cells was continuous in the normal control group, the elastic fibers were intact in the subcutaneous layer, and the smooth muscle layer was arranged neatly. LPS can shed some of the pulmonary artery endothelial cells, break the subcutaneous elastic fibers, and disorder the smooth muscle layer structure. Compared with LPS group, the injury of pulmonary artery wall in LPS+NaHS group was ameliorated. The morphology of pulmonary artery wall was normal in NaHS group. It is showed that some endothelial cells of pulmonary artery were missing in LPS group by Scanning electron microscopy. The morphology of pulmonary artery endothelial cells in LPS+NaHS group was similar to that in the control group: slightly widened intercellular space was observed, and no cell exfoliation was observed. Conclusion: These results suggest that exogenous H2S can protect pulmonary artery endothelial cells and regulate the reactivity changes of pulmonary artery during ES, which may be one of the mechanisms reducing PAH in ES rabbits.

Mineralocorticoid Receptor-Dependent Impairment of Baroreflex Contributes to Hypertension in a Mouse Model of Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. The paucity of good animal models hinders our understanding of the pathophysiology of PA and the hypertensive mechanism of PA remains incompletely known. It was recently reported that genetic deletion of TWIK-related acid-sensitive potassium-1 and potassium-3 channels from mice (TASK-/-) generates aldosterone excess and mild hypertension. We addressed the hypertensive mechanism by assessing autonomic regulation of cardiovascular activity in this TASK-/- mouse line that exhibits the hallmarks of PA. Here, we demonstrate that TASK-/- mice were hypertensive with 24-h ambulatory arterial pressure. Either systemic or central blockade of the mineralocorticoid receptor (MR) markedly reduced elevated arterial pressure to normal level in TASK-/- mice. The response of heart rate to the muscarinic cholinergic receptor blocker atropine was similar between TASK-/- and wild-type mice. However, the responses of heart rate to the ß-adrenergic receptor blocker propranolol and of arterial pressure to the ganglion blocker hexamethonium were enhanced in TASK-/- mice relative to the counterparts. Moreover, the bradycardiac rather than tachycardiac gain of the arterial baroreflex was significantly attenuated and blockade of MRs to a large degree rescued the dysautonomia and baroreflex gain in TASK-/- mice. Overall, the present study suggests that the MR-dependent dysautonomia and reduced baroreflex gain contribute to the development of hyperaldosteronism-related hypertension.

Comparison of the effects of chronic intermittent hypobaric hypoxia and continuous hypobaric hypoxia on hemodynamics in rats.

The aim of this study is to investigate the effects of chronic intermittent hypobaric hypoxia (IHH) and chronic continuous hypobaric hypoxia (CHH) on hemodynamics under basic normoxia and acute hypoxia conditions and to find the difference of two types of chronic hypoxia. Forty adult male Sprague-Dawley (SD) rats were randomly divided into 5 groups: Control group (CON), 28 days IHH group (IHH28), 42 days IHH group (IHH42), 28 days CHH group (CHH28) and 42 days CHH group (CHH42). The rats in IHH groups were treated with intermittent hypoxia (11.1% O2) mimicking 5 000 m altitude in a hypobaric chamber for 28 or 42 d, 6 h a day, respectively. The rats in CHH groups lived in the hypobaric chamber with the same degree of hypoxia like IHH rats except half an hour in normoxia each day for feeding and cleaning. The body weight of rats was measured once a week. The parameters in hemodynamics, such as mean artery blood pressure (MAP), heart rate (HR), left ventricular systolic pressure (LVSP), maximum change rate of left ventricular pressure (+/-LVdP/dt(max)) were recorded under basic normoxia and acute hypoxia conditions through catheterization technique. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium of rats were measured by biochemical method. The weights of whole heart, left and right ventricles were measured separately. The results showed: (1) The basic HR and MAP in CHH42 rats were lower than those in CON, IHH and CHH28 rats (P<0.05). (2) IHH showed a cardioprotection against acute hypoxia and reoxygenation injury, manifested as the result that the changes of HR, MAP, LVSP, and +/- LVdP/dt(max) were smaller than those in CON rats during acute hypoxia and reoxygenation. CHH showed a rather strong cardioprotection during acute hypoxia, manifested as the result that the decreases of HR, MAP, LVSP, and +/- LVdP/dt(max)were much smaller, but it did damage during reoxygenation, manifested as the result that the recovery of hemodynamics was the worst among three groups (P<0.05). (3) The antioxygenation of heart was increased in both IHH and CHH rats compared with that in CON rats manifested by the increased SOD activity and decreased MDA content (P<0.05, P<0.01). (4) IHH had no effect on heart weight, but CHH rats showed an obvious right ventricular hypertrophy compared with CON and IHH animals (P<0.01). The result indicates that IHH can induce a more effective cardioprotection with no much side effect, which might have a potential value for practical use.

[Pluripotential differentiation of QY1 bone marrow mesenchymal stem cell line].

OBJECTIVE: To explore the ability of QY1 bone marrow mesenchymal stem cell (MSCs) line cells to differentiate into adipocytes, chondrocytes, osteoblasts, cardiac myocytes,vascular endothelial cells, and neural cells in vitro. METHODS: The QY1 cells at passage 5 were treated with the adipogenic medium, the chondrogenic medium and the osteogenic medium, 5-azacytidine, vascular endothelial growth factor and neural cell medium (revulsant 1 was 10 mmol/L beta-mercaptoethanol; revulsant 2 was 2%dimethylsulfoxide and 10(-8)mol/L dexamethasone) in culture respectively in vitro. The differentiated cells were identified by staining, immunohistochemistry and RT-PCR. RESULTS: The differentiated cells induced by the adipogenic medium formed adipocytes and contained fat lipid droplets, which were stained positively with Sudan III after 21 days of culture. The differentiated cells induced by the chondrogenic medium formed chondrogenic nodules, which were stained positively by Alcian blue at pH 1.0 after 21 days of culture. The differentiated cells induced by the osteogenic medium formed osteogenic nodules, which were stained positively by Von Kossa staining after 35 days of culture, and the secretion of a calcified extracellular matrix as black nodules was observed. The differentiated cells treated with 10 micromol/L 5-azacytidine could beat spontaneously and formed myotube structures,which were identified by the positive immunohistochemistry staining with anti-alpha-sarcomeric antibody and anti-Cx-43 antibody. The expression of alpha-myosin heavy chain was also observed by RT-PCR. The differentiated cells treated with 50 ng/mL vascular endothelial growth factor could form vascular endothelial cells and vascular endothelial web like structure, which were identified by the positive immunohistochemistry staining with CD31 and Factor VIII. The differentiated cells induced by revulsant 1 were positive in the immunohistochemistry staining with neuron-specific nuclear protein, while the expression of glial fibrillary acidic protein was negative. The differentiated cells induced by revulsant 2 were positive in the immunohistochemistry staining with glial fibrillary acidic protein, while the expression of neuron-specific nuclear protein was negative. CONCLUSION: QY1 bone marrow mesenchymal stem cell line has the ability to differentiate into adipocytes, chondrocytes, osteocytes, cardiomyocytes, vascular endothelial cells, neurons and neural glial cells in vitro. A bone marrow mesenchymal stem cell line cell can at least differentiate into 7 types of cells, which come from mesoderm and ectoderm.

Protective Effects of Chronic Intermittent Hypobaric Hypoxia Pretreatment against Aplastic Anemia through Improving the Adhesiveness and Stress of Mesenchymal Stem Cells in Rats.

Aplastic anemia (AA) is a common malignant blood disease, and chronic intermittent hypobaric hypoxia (CIHH) has a beneficial effect against different diseases. The aim of the present study was to investigate the protective effect of CIHH against AA and underlying mechanisms. 5-Fluorouracil and busulfan treatment induced AA model in rats with reduction of hematological parameters and bone marrow tissue injury and decrease of the colony numbers of progenitor cells. CIHH pretreatment significantly reduced the incidence rate of AA and alleviated above symptoms in AA model. The adhesive molecules of bone marrow mesenchymal stem cells (BMMSCs) in AA model, VLA-4, VCAM-1, and ICAM-1 were upregulated, and those of CD162 and CD164 were downregulated by CIHH pretreatment. The expressions of HIF-1α and NF-κB in BMMSCs were also decreased through CIHH pretreatment. Overall, the results demonstrated for the first time that CIHH has an anti-AA effect through improving the adhesiveness and stress of mesenchymal stem cells in rats. CIHH could be a promising and effective therapy for AA.

Chronic intermittent hybobaric hypoxia protects against cerebral ischemia via modulation of mitoKATP.

OBJECTIVE: Providing adequate protection against cerebral ischemia remains an unrealized goal. The present study was aimed at testing whether chronic intermittent hypobaric hypoxia (CIHH) would have protective effects against cerebral ischemia and investigating the potential role of mitochondrial membrane ATP-sensitive potassium channel (mitoKATP) in this effect. METHODS: Ischemia was induced in rats by occlusion of bilateral common carotid arteries for 8min on day 2 after bilateral vertebral arteries were permanently electrocauterized and CIHH was simulated in a hypoxic chamber. Learning and memory impairments were analyzed using the Morris water maze. The delay neuronal death (DND) in the hippocampus CA1 was observed by thionine staining. The expression of the two subunits of mitoKATP, SUR1 and Kir 6.2, and the concentration of cytochrome c (Cyt c) were observed by Western blotting. The mitochondrial membrane potential (Δym) was determined by flow cytometry. Morphological changes of the mitochondria were investigated by electron microscopy. The antagonist of mitoKATP, 5-hydroxydecanoate (5-HD), was used to demonstrate the involvement of mitoKATP. RESULTS: CIHH pretreatment ameliorated the learning and memory impairments produced by ischemia, concomitant with reduced DND in the hippocampus CA1 area. Expression levels of SUR1 and Kir6.2 both increased for at least one week after CIHH pretreatment. Levels of the two subunits were higher in the CIHH pretreatment combined with ischemia group than the ischemia only group at 2 d and 7 d after ischemia. Furthermore, the concentration of Cyt c was decreased in mitochondria and increased in the cytoplasm after ischemia which was prevented by CIHH. The decrease of Δψm and the destruction of mitochondrial ultrastructure were both rescued by CIHH pretreatment. The above protective effects of CIHH were blocked by 5-HD intraperitoneal injection 30min before ischemia. CONCLUSION: CIHH pretreatment can reduce cerebral ischemic injury, which is mediated by upregulating the expression and activity of mitoKATP.

Chronic intermittent hypobaric hypoxia ameliorates endoplasmic reticulum stress mediated liver damage induced by fructose in rats.

AIM: High-fructose intake induces nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypobaric hypoxia (CIHH) has beneficial effects on the body. We hypothesized that CIHH has protective effects on the impaired hepar in fructose-fed rats. MAIN METHODS: Sprague-Dawley rats (male, 160-180 g) were randomly divided into 4 groups: control group (CON), fructose group (FRUC, 10% fructose in drinking water for 6 weeks), CIHH group (simulated 5000m altitude, 6h per day for 6 weeks), and CIHH plus fructose groups (CIHH-F). Histopathology of liver, arterial blood pressure, blood biochemicals, hepatocyte apoptosis, and marker proteins of endoplasmic reticulum stress (ERS) were measured. KEY FINDINGS: The arterial blood pressure, body mass index, abdominal fat weight and liver weight were increased in FRUC rats but not in CIHH-F rats. Likewise, the serum glucose, insulin, insulin C peptide, triglyceride (TG) and total cholesterol (TC) were elevated in FRUC rats but not in CIHH-F rats after fasting 12h. Meanwhile, the hepatic steatosis and hepatocyte apoptosis occurred in FRUC rats but not in CIHH-F rats. Finally the expression of ERS markers including GRP78 (glucose-regulated protein78), CHOP (C/EBP Homologous Protein), and caspase-12 in hepatic tissue were up-regulated in FRUC rats, but such up-regulation was not observed in CIHH-F rats. SIGNIFICANCE: Our results suggest that CIHH protect hepar against hepatic damage through inhibition of ERS in fructose-fed rats. CIHH might be the new therapy for NAFLD.

[The effect of emodin on the contraction of isolated jejunum smooth muscle of rats].

OBJECTIVE: To investigate the effect of emodin on the contraction of jejunum smooth muscle and its underlying mechanisms. METHODS: Rats were randomly divided into 7 groups (n = 6): control group, emodin group (1, 5, 10, 20 micromol/L), propranolol (PRO) plus emodin group, glibenclamide (GLI) plus emodin group, NG-Nitro-L-arginine Methyl Ester (L-NAME) plus emodin group, calcium free control group and calcium free emodin group. The rats were sacrificed by cervical dislocation and the small intestine was isolated. The jejunum segment specimens were mounted on an Organ Bath System with a tension transducer. The effect of emodin on contraction of jejunum smooth muscle was measured by BL-420E+ biological signal processing system and the amplitude (AM), tension (TE) and frequency (FR) of contraction were determined. RESULTS: (1) Emodin inhibited the tension and amplitude of jejunum smooth muscle contraction in a dose-dependent manner (P < 0.05, P < 0.01) while the frequency was not obviously influenced. (2) PRO (P < 0.05) or GLI (P < 0.01) partly abolished the inhibitory effect of emodin on jejunum smooth muscle. (3) L-NAME had no obvious effect on the inhibitory effect of emodin. (4) Emodin attenuated the contraction of jejunum smooth muscle induced by calcium chloride application into calcium free K-H solution (P < 0.01). CONCLUSION: Emodin obviously inhibits the amplitude and tension, while has no influence on the frequency of jejunum smooth muscle contraction in rats. Activation of beta adrenergic receptor, open of ATP sensitive potassium channels, and inhibition of the extracellular calcium influx through calcium channels of smooth muscle cell membrane might be involved in the process.

[Influences of Panax notoginsenosid on spontaneous contraction of small intestine smooth muscle of rabbits in vitro].

OBJECTIVE: To observe the influences of Panax notoginsenosid(a compound of Chinese Traditional Medicine) on the spontaneous contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism. METHODS: The influences of Panax notoginsenosid on the spontaneous contraction of small intestine in intacted rabbits(male or female) after the isothermal perfuse of small intestine in vitro were observed. Bay K8644 and nitro-L-arginine methylester (L-NAME) were added to the normal Tyrode's solution respectively before Panax notoginsenosid. In the Ca2+ free Tyrode's solution, rynodine was added before Panax notoginsenosid. The mechanism of Panax notoginsenosid was studied. RESULTS: Panax notoginsenosid reduced the amplitude of contraction of small intestine smooth muscle in rabbits in a does-depended manner. Bay K8644 and L-NAME could completely block the inhibition of Panax notoginsenosid on the contraction of small intestine smooth muscle. Panax notoginsenosid inhibited significantly the intracellular calcium-depended contraction induced by rynodine in the Ca2+ free Tyrode's solution. CONCLUSION: Panax notoginsenosid inhibits significantly the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that inhibit extracellular Ca2+ inflowing via cell membrane and intracellular Ca2+ releasing via sarcoplasmic reticulum.

8-Hydroxyquinoline derivatives induce the proliferation of rat mesenchymal stem cells (rMSCs).

A series of 8-hydroxyquinoline derivatives with different substituted groups at 2- or 5-position have been synthesized and characterized. Their effects on the proliferation of the rat marrow-derived mesenchymal stem cells (rMSCs) have been evaluated by MTT assay and flow cytometry. We also analyzed the ability of these compounds to regulate the proliferation of rMSCs and the relationship with the structures of 8-hydroxyquinoline. Compounds 8-11, in which, the vinyl-substituents are on the 2-position of 8-hydroxyquinoline, appear to be able to induce the proliferation of rMSCs. These results show that compounds 8-11 provide a kind of new substances for regulating the proliferation of rMSCs.