Anti-inflammatory Therapy Progress in Major Adverse Cardiac Events after PCI: Chinese and Western Medicine / 中国结合医学杂志

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.

Terpenoids isolated from Viburnum ternatum / 中国中药杂志

Four iridoids (1-4), five iridoid glucosides (5-9), and three triterpenoids (10-12) were isolated from the ethyl acetate soluble fraction of 70% Me2CO extract of the aerial parts of Viburnum ternatum through various column chromatographies over silica gel, ODS, Sephadex LH-20 and MCI. Their structures were elucidated as ternatumin A (1), 2,9-dioxatricyclo[4.3.1.03，7]decanes (2), 7,10,2'-triacetylsuspensolide F (3), 7,10,2',3'-tetraacetylsuspensolide F (4), viburtinoside IV (5), viburtinoside II (6), viburtinoside B (7), luzonoside A (8), luzonoside B (9), 2α,3β,24-trihydroxy-12-ursen-28-oic acid (10), 6-hydroxy-20(29)-lupen-3-one (11), and pomalic acid (12) based on the their chromatographic properties, chemical and physicochemical methods, and spectroscopic data. Compound 1 was a new compound and compounds 3-12 were isolated from this plant for the first time. Furthermore, we note here the first isolation of compound 2 as a new natural product.

The role of NO resulted from neuronal nitric oxide synthase in the metabotropic glutamate receptor2/3 mediated-brain ischemic tolerance / 中国应用生理学杂志

<p><b>AIM</b>To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3 mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), the present study is undertaken to observe the influences of alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of nNOS during the induction of the brain ischemic tolerance based on confirming the blocking effect of MTPG on the induction of the tolerance.</p><p><b>METHODS</b>Thirty-six Sprague-Dawley rats, whose vertebral arteries were permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+ ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of nNOS expression in the hippocampal CA1 subregion of the rats.</p><p><b>RESULTS</b>The expression of nNOS showed moderate and extreme up-regulation in the CIP and ischemia groups, respectively, compared to the sham group. The preceded CIP blocked in certain extent the extreme up-regulation of nNOS induced by brain ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+ ischemic insult group, the expression of nNOS was stronger than that in the MTPG + CIP group, and the up-regulation was accompanied with obvious delayed neuronal death. Discussion concerned illustrated that the relative intensive up-regulation of nNOS in this group might be attributed to brain ischemia other than MTPG.</p><p><b>CONCLUSION</b>NO resulted from nNOS participated the induction of mGluR2/3 mediated-brain ischemic tolerance as a downstream molecule of activation of mGluR2/3 during CIP.</p>

Effect of compound EXP-2528 on angiotensin II-induced E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells in vitro / 药学学报

The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang II type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1 x 10(-7) mol x L(-1) Ang II. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang II-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang II upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.

The effect of time parameters of cerebral ischemic preconditioning on its protective effect against global cerebral ischemic injury in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult.</p><p><b>METHODS</b>Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus.</p><p><b>RESULTS</b>No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05).</p><p><b>CONCLUSION</b>Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.</p>

Protective effects of hydroxyethylpuerarin against brain astrocytes injury induced by hydrogen peroxide / 药学学报

<p><b>AIM</b>To study the protective effects of hydroxyethylpuerarin against the injury of astrocytes induced by hydrogen peroxide (H2O2).</p><p><b>METHODS</b>Experiments were performed with cells from passage 4. Plasma membrane integrity was measured by lactate dehydrogenase (LDH) release. The occurrence of apoptosis was measured by flow cytometry. The glutamate uptake of astrocytes was studied with [3H]-glutamate incorporation. Intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assessed by automatic biochemistry analyzer.</p><p><b>RESULTS</b>Compared with H2O2 injured group, the occurrence of apoptosis, levels of LDH release and intracellular MDA of astrocytes reduced in hydroxyethylpuerarin pre-treated groups, but the glutamate uptake and intracellular SOD activity of astrocytes increased.</p><p><b>CONCLUSION</b>Hydroxyethylpuerarin could reduce the occurrence of apoptosis and improve neurotrophic function of astrocytes, which may be related with its antioxidant effects during oxidative stress.</p>

Protective effects of hydroxyethylpuerarin on cultured bovine cerebral microvascular endothelial cells damaged by hydrogen peroxide / 药学学报

<p><b>AIM</b>To observe the damages induced by hydrogen peroxide in cultured bovine cerebral microvascular endothelial cells (BCMEC) and evaluate the protective effects of hydroxyethylpuerarin on hydrogen peroxide-injured BCMEC.</p><p><b>METHODS</b>BCMEC were cultured and transferred into modified Eagle medium (MEM). The viability of cells was detected by MTT assay. Cell injury was determined by lactate dehydrogenase (LDH) activity in the extracellular medium. Flow cytometry was employed to observe the occurrence of apoptosis. Morphologic changes of cells were visualized under phase contrast and electron microscopes.</p><p><b>RESULTS</b>Hydrogen peroxide (200 micromol x L(-1) for 4 hours) inhibited the viability of cultured BCMEC and stimulated LDH release. Hydrogen peroxide (100 micromol x L(-1) for 4 hours) induced the occurrence of apoptosis. Hydroxyethylpuerarin was shown to increase the survival rate and decrease the activity of LDH of BCMEC damaged by hydrogen peroxide. Hydroxyethylpuerarin was also found to protect BCMEC against apoptosis induced by hydrogen peroxide.</p><p><b>CONCLUSION</b>Hydrogen peroxide induces BCMEC injury either by apoptosis or through necrosis. Hydroxyethylpuerarin protects BCMEC against hydrogen peroxide-induced injury in a concentration-dependent manner. Its antioxidant effects might be involved as the mechanism protection.</p>

Limb ischemic preconditioning decreases hippocampal ischemia/reperfusion injuries in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of limb ischemic preconditioning (LIP) on cerebral ischemia/reperfusion injuries.</p><p><b>METHODS</b>Thirty six wistar rats, of which bilateral vertebral arteries were occluded permanently, were randomly divided into the following 6 groups: control group, cerebral ischemic group, limb ischemic group, LIP 0 d group (cerebral ischemia was given immediately after LIP), LIP 1 d group (cerebral ischemia was given 1 d after LIP) and LIP 2 d group (cerebral ischemia was given 2 d after LIP). Global cerebral ischemia was performed by four vessels occlusion in rats. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in a interval of 10 min. The histological grade and pyramidal neuronal density in the CA1 hippocampus were measured to quantitate the degree of hippocampal injury under thionin staining.</p><p><b>RESULTS</b>The histological grade was increased and the pyramidal neuronal density was decreased in the CA1 hippocampus of the cerebral ischemic group (P < 0.01). The damage of the CA1 hippocampus in LIP 0 d group was significantly diminished, which represented by decreased histological grade and increased neuronal density compared with the cerebral ischemic group (P < 0.01). But the CA1 hippocampus still showed obvious injuries in the LIP 1 d and LIP 2 d group.</p><p><b>CONCLUSION</b>LIP performed immediately prior to cerebral ischemia could confer obvious protective effects on CA1 hippocampus against cerebral ischemia/reperfusion injuries. But LIP performed 1 d and 2 d prior to cerebral ischemia could not afford the protection against injuries induced by cerebral ischemia/reperfusion.</p>

Limb ischemic preconditioning attenuates apoptosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats / 生理学报

The purpose of this study was to investigate the effects of limb ischemic preconditioning (LIP) on apoptosis of pyramidal neurons in the CA1 hippocampus induced by global cerebral ischemia-reperfusion in rats. Forty-six rats whose bilateral vertebral arteries were occluded permanently were assigned to one of four groups: sham group, limb ischemia group, cerebral ischemia group and LIP group. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in an interval of 10 min. Global cerebral ischemia was underwent by occluding the bilateral common carotid arteries for 8 min immediately after LIP. Assays for apoptosis of the hippocampal neurons were biologically and morphologically performed using gel electrophoresis, TUNEL and AO/EB staining. Characteristic DNA ladder was clearly visualized with gel electrophoresis in the hippocampus in cerebral ischemia group, but not in LIP group. The number of TUNEL-positive cells in the CA1 hippocampus was significantly reduced by LIP from 69.8+/-12 (cerebral ischemia group) to 17.8+/-5.8 (P<0.01). AO/EB staining also showed a reduction of apoptosis in LIP group compared with cerebral ischemia group. These results suggest that LIP can inhibit hippocampal neuronal apoptosis induced by cerebral ischemia-reperfusion, which contributes to the protection against the delayed neuronal death induced by cerebral ischemic insult.

Effects of the metabotropic glutamate receptor ligand(s)-4C3HPG on the induction of brain ischemic tolerance in the rat / 中国应用生理学杂志

<p><b>AIM</b>To explore roles of metabotropic glutamate receptor1/5 (mGluR1/5) in the induction of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), influences of mGluR1/5 ligand (s)-4-carboxy-3-hydroxy- phenylglycine ((s)-4C3HPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed.</p><p><b>METHODS</b>Thionin staining and GFAP immunohistochemistry staining in rat 4 vessel occlusion (4VO) brain ischemic model was used. Thirty-six rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 4 groups: sham group; ischemic insult group, BIT group and (s)-4C3HPG group. According to dosages of (s)-4C3HPG used, the (s)-4C3HPG group, was further divided into 0.2 mg, 0.04 mg and 0.008 mg subgroups. All the rats were killed 7 d after the operation or the final ischemic treatment.</p><p><b>RESULTS</b>(1) The ischemic insult for 8 min increased the histological grade (HG), decreased the pyramidal neuronal density (ND) and increased the expression of GFAP significantly (P < 0.05 vs sham) (2) The CIP prevented the above injury changes in the BIT group. (3) The protective effects of the CIP were blocked by (s)-4C3HFG, as manifested by significant increases in HG and decreases in ND in the (s)-4C3HPG group (P < 0.05 vs sham and BIT groups). The changes were proportional with the dosages of (s)-4C3HPG used.</p><p><b>CONCLUSION</b>(s)-4C3HPG could block the induction of BIT induced by CIP, suggested that mGluR1/5 participate in the induction of BIT.</p>

Effect of nitric oxide synthase inhibitor L-NAME on the induction of brain ischemic tolerance in rats / 生理学报

To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.

Effects of alpha-methyl-(4-tetrazolyl-phenyl) glycine on the induction of hippocampal ischemic tolerance in the rat / 生理学报

To explore the role of metabotropic glutamate receptor 2/3 mGluR 2/3 in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP. In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent. (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.