Chronic intermittent hypobaric hypoxia ameliorates myocardial apoptosis through inhibiting mitochondrial pathway in rats with metabolism syndrome / 中国药理学通报

Aim To confirm the inhibitory effect of chronic intermittent hypobaric hypoxia ( CIHH) on my-ocardial apoptosis induced by metabolism syndrome ( MS) , and to investigate its mechanism. Methods A rat model of MS induced by fructose was used. The blood pressure and the plasma content of glucose, tri-glyceride, cholesterol, and insulin after 12 h fasting were detected. HE stain were used to detect the cardi-ac structure. The TUNEL staining and activity of caspase-3 were used to detect the apoptosis of myocar-dium. The protein expression of Bcl-2 and Bax was detected by Western blot . Results Compared with the control rats, the blood pressure and the plasma content of glucose, triglyceride, cholesterol, and insu-lin were all increased in rats with MS. In rats with MS, the impairment of cardiac structure and the increase of apoptosis were also observed. The protein expression of Bcl-2 was significantly down-regulated, and that of Bax was significantly up-regulated in MS rats. The ratio of Bcl-2/Bax was also significantly decreased. Interest-ingly, CIHH could ameliorate all of the above issues. There was no significant difference between control group and CIHH group. Conclusion CIHH may im-prove the increased apoptosis in rats with MS via inhib-iting the mitochondrial pathway of apoptosis. This stud-y might provide new targets for therapy and the preven-tion of MS patients.

The effect of emodin on the contraction of isolated jejunum smooth muscle of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of emodin on the contraction of jejunum smooth muscle and its underlying mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSION</b>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.</p>

Chronic intermittent hypobaric hypoxia enhances vasodilative effects of paeonol on isolated thoracic aorta rings of rats / 中国药理学通报

Aim To investigate the effect of chronic intermittent hypobaric hypoxia ( CIHH) on the paeonol induced vasomotion of isolated rat ’ s thoracic aorta rings and its underlying mechanisms. Methods Spra-gue-Dawlay ( SD ) rats were randomly divided into 2 groups: control group ( CON ) and CIHH treatment group ( CIHH) . CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 hours daily for 28 days. CON rats lived in the same en-vironment as CIHH animals except hypoxia. Organ bath technique was used to observe the effect of pae-onol on isolated thoracic aorta rings of rats. Results There were no significant differences of noradrenaline ( NE )- and KCl-induced contraction in thoracic aorta rings among CIHH and CON rats;CIHH enhanced va-sodilative effects of paeonol on isolated thoracic aorta rings of rats; the vasodilative effects on CIHH rats could be partly decreased by β-receptor blocker prop-ranolol,ATP-sensitive potassium channel ( KATP ) bloc-ker glibenclamide and NO synthase inhibitor L-NAME. Paeonol significantly inhibited NE-induced intracellular and extracellular calcium-dependent contraction in CIHH rats. Paeonol didn ’ t inhibit NE-induced con-traction by intracellular calcium release and its inhibi-tory effect couldn ’ t be blocked by glibenclamide in CON. Vasodilative effects of paeonol couldn ’ t be re-versed by indomethacin, a cyclooxygenase inhibitor, in CIHH and CON rats. Conclusion CIHH significantly enhances vasodilative effects of paeonol on isolated tho-racic aorta rings of rats. Besides promoting the signa-ling pathway of paeonol in CON, CIHH significantly enhances vasodilative effects of paeonol via activating KATP and inhibiting Ca2+ release from sarcoplasmic re-ticulum.

Opioid receptors mediate enhancement of ACh-induced aorta relaxation by chronic intermittent hypobaric hypoxia / 生理学报

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.

Analyses on positive influence of harmonous development of traditional Chinese medicine compounds' researchs and patent protection / 中国中药杂志

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.

Cluster analysis on authorized patents of compound traditional Chinese medicines with different efficacy in 2010 / 中国中药杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>The samples were classified into four groups by clustering methods, each has significant difference in authorized patents' number and authorized time interval with others.</p><p><b>CONCLUSION</b>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.</p>

Influences of Panax notoginsenosid on spontaneous contraction of small intestine smooth muscle of rabbits in vitro / 中国应用生理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Comparison of the effects of chronic intermittent hypobaric hypoxia and continuous hypobaric hypoxia on hemodynamics in rats / 生理学报

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 / 中南大学学报(医学版)

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.