The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.
Animals ; Intestinal Absorption ; Intestines ; Isoproterenol ; Myocardial Ischemia/chemically induced* ; Polygonum ; Rats ; Rats, Sprague-Dawley

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Animals ; Kidney ; Acute Kidney Injury/chemically induced* ; Ischemia ; Reperfusion Injury/drug therapy* ; Autophagy ; Reperfusion

Ergotamine-induced limb ischemia is an extremely rare case. We present a case of a 64-year-old man, who developed ischemia on the right upper extremity due to long-term use of Ergot for migraine headache. Angiography revealed diffused, smooth, and tapered narrowing of the brachial artery. The patient was successfully treated with intravenous nitroprusside.
Arm/*blood supply ; *Brachial Artery/radiography ; Ergotamine/*adverse effects ; Humans ; Infusions, Intravenous ; Ischemia/*chemically induced/drug therapy/radiography ; Male ; Middle Aged ; Migraine/drug therapy ; Nitroprusside/administration & dosage

PURPOSE: The purpose of this study was to determine the effect of DHEA on hindlimb muscles(soleus, plantaris and gastrocnemius) in a focal brain ischemia model rat. METHOD: Twenty-seven male Sprague-Dawley rats were randomly divided into three groups: CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), or SHNS(sham + normal saline). Both the CINS and CIDH groups underwent a transient right middle cerebral artery occlusion operation. In the SHNS group, a sham operation was done. 0.34mmol/kg DHEA was administered daily by an intraperitoneal injection for 7days. RESULT: The muscle weight, muscle fiber cross-sectional area of the Type I muscle fiber of soleus and Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of gastrocnemius, and muscle strength in the CINS group decreased compared with the SHNS group. The muscle weight, muscle fiber cross-sectional area of the Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of soleus, and muscle strength in the CIDH group increased compared with the CINS group. CONCLUSION: It was identified that muscle atrophy could be induced during 7 days after a cerebral infarction, and DHEA administration during the early stages of a cerebral infarction might attenuate muscle atrophy.
Animals ; Brain Ischemia/*pathology ; Dehydroepiandrosterone/*pharmacology ; Hindlimb ; Male ; Muscle, Skeletal/*drug effects/pathology ; Muscular Atrophy/chemically induced ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the protective effect of noninvasive limb ischemic preconditioning (N-LIP) on acute lung injury (ALT) induced by lipopolysaccharide (LPS) in rats. METHODS: Fifteen female SD rats were randomly divided into a control group, an acute lung injury group (ALI group), an acute lung injury and noninvasive limb ischemic preconditioning group (ALI+N-LIP group). After ALI rats were treated with N-LIP, the changes of airway resistance (AR) and dynamic compliance (Cdyn) were tested by invasive pulmonary function system and recorded. Blood samples and bronchoalveolar lavage fluid (BALF) were collected, the amounts of white blood cell (WBC) in BALF were counted by cytometry, and the level of lactate dehydrogenase (LDH) in BALF was also examined by automatic biochemistry analyzer. The level of serum superoxide dismutase (SOD) and malondialdehyd (MDA) was examined by chromatometry. The lung tissues were acquired to observe the expression of pulmonary surfactant-associated protein-A (SP-A) and pathological changes. RESULTS: After being stimulated by methacholine (Mch), the increasing rate of AR and decreasing rate of Cdyn in the ALI+N-LIP group were less than those in the ALI group (P<0.01). The levels of WBC and LDH in BALF in the ALI+N-LIP group were much lower than those in the ALI group (P<0.05). Meanwhile, the activity of serum SOD in the ALI+N-LIP group was higher, and the level of serum MDA was lower than that in the ALI group (P<0.05). The expression of SP-A in the lung tissue in the ALI+N-LIP group was the highest in the 3 groups, while that in the ALI group was the weakest (P<0.01). Injury of the lung tissue in the ALI+N-LIP group was less than that in the ALI group, but more severe than that in the control group. CONCLUSION N-LIP has protective effect on acute lung injury induced by LPS in rats. The possible mechanism is related to improving the secretion of SP-A and antioxidation.
Acute Lung Injury ; chemically induced ; complications ; prevention & control ; Animals ; Female ; Ischemia ; complications ; physiopathology ; Ischemic Preconditioning ; methods ; Lipopolysaccharides ; Lower Extremity ; blood supply ; Random Allocation ; Rats ; Rats, Sprague-Dawley

To investigate the effects of triptolide on inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats.The rat model of focal cerebral ischemia/reperfusion injury was established according to Longa's method. A total of 80 SD rats were randomly divided into 5 groups:normal control, sham group, DMSO group, middle cerebral artery occlusion (MCAO) group, and MCAO with tripolide treatment group. TTC staining was used to examine the site and volume of cerebral infarction, and Longa score was employed for neurological disorders measurement. Number of astrocytes was measured by fluorescence staining, and neuronal apoptosis was determined by TUNEL staining. The expressions of inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and NF-κB proteins were detected by immunohistochemistry, and the expression of iNOS, COX-2 mRNA was detected by real-time PCR.Compared with DMSO group and MCAO group, brain edema was improved (80.03±0.46)% (<0.05), infarct volume was reduced (8.3±1.4)% (<0.01), Longa score was decreased (1.38±0.20,<0.05) in triptolide treatment group. Meanwhile triptolide also dramatically reduced the number of GFAP-positive astrocytes (<0.05), alleviated protein expression of COX-2 (91.67±1.31), iNOS (95.24±5.07) and NF-κB (75.03±2.06) triggered by MCAO (all<0.05), and induced a down-regulation of cell apoptosis as showed by TUNEL assay (64.15±3.52,<0.05).Triptolide can reduce the cerebral infarction volume, attenuate brain edema and ameliorate the neurological deficits induced by cerebral ischemia-reperfusion injury rats, indicating that it might be used as a potential anti-inflammatory agent.
Animals ; Apoptosis ; drug effects ; Astrocytes ; Brain Edema ; drug therapy ; Brain Injuries ; chemically induced ; drug therapy ; Brain Ischemia ; chemically induced ; Cyclooxygenase 2 ; drug effects ; Diterpenes ; pharmacology ; Down-Regulation ; drug effects ; Epoxy Compounds ; pharmacology ; Infarction, Middle Cerebral Artery ; chemically induced ; drug therapy ; Inflammation ; drug therapy ; Male ; NF-kappa B ; drug effects ; Nitric Oxide Synthase Type II ; drug effects ; Phenanthrenes ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; chemically induced ; drug therapy

OBJECTIVETo study comparatively the effect of Guanxin II and its constituents, including Salvia, Red Peony root, Chuanxiong, Safflower and Dalbergia wood, in scavenging active oxygen free radical (OFR) to explore their mechanism in overcoming the experimental acute ischemic myocardial injury and protecting myocardial tissue.

METHODSThe experimental acute myocardial ischemic model was established by intraperitoneal injection of pituitrin to rats. OFR level in animal heart tissue was directly measured with low-temperature electron paramagnetic resonance (EPR) spectrometer.

RESULTSThe pathological examination of HE stained slide of myocardial tissue and electrocardiography of model animal showed that typical changes of acute myocardial ischemia occurred in myocardial tissue, EPR showed that OFR level in myocardial tissue increased abnormally. The ethanol extract of Guanxin II and its constituents could lower the increased OFR level close to normal, thus to alleviate the myocardial damage.

CONCLUSIONOverproduction of OFR could induce damage of heart tissue, its level could be measured directly using low temperature EPR. One of the molecular mechanisms of Guanxin II and its constituents in antagonizing and repairing myocardial damage is to scavenge the abnormal increased active OFR in tissue. This study has provided a basis for further studying the mechanism of Chinese composite recipes and their constituents.

Animals ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Electron Spin Resonance Spectroscopy ; Free Radical Scavengers ; pharmacology ; Free Radicals ; metabolism ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; Myocardium ; metabolism ; Pituitary Hormones, Posterior ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the molecular mechanism of effect of Sini Decoction (SND) on myocardial endothelin (MET) in myocardial ischemic rats.

METHODSSprague-Dawley rats were randomly divided into 3 groups, the normal control group, the ischemia group and the SND group. Myocardial ischemia was produced by pituitrin in the latter two groups. The content, immunohistochemical assay and gene expression of MET-1 were determined in all the three groups and compared.

RESULTSThe content of MET in the SND group was significantly lower than that in the ischemia group (P < 0.01). Immunohistochemical examination showed that MET-1 was mainly located at the cardiac muscle cells and vascular endothelial cells with the grey scale obviously lower in the ischemia group than that in the control group and the SND group (P < 0.01). While RT-PCR showed that the grey scale of PCR product band in the ischemia group was significantly higher than that in the other two groups (P < 0.01).

CONCLUSIONSND could significantly lower MET content, it may be related to the effect of SND in inhibiting MET-1 gene expression and protein synthesis.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; biosynthesis ; genetics ; Female ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; Myocardium ; metabolism ; Phytotherapy ; Pituitary Hormones, Posterior ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIMTo determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.

METHODSSlow microinjection of endothelin-1 (120 pmol in 6 microL, for > 6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO-1078 (0.1 mg.kg-1) was i.p. injected 1 h before endothelin-1 injection. Neurological symptoms, brain edema, brain infarction size, and the survival neurons in cortex and striatum were observed 24 h after ischemia.

RESULTSIntracerebral microinjection of endothelin-1 induced remarkable neurological symptoms, brain infarction, brain edema, and decrease of survival neurons in the cortex and striatum. In rats pretreated with ONO-1078, endothelin-1-induced brain edema and brain infarction size were decreased. The numbers of survival neurons in striatum and cortex were increased significantly. The neurological symptoms were improved but not significantly.

CONCLUSIONONO-1078 possesses neuroprotective effect against cerebral ischemic injury induced by endothelin-1, therefore, leukotrienes may play a role in the injury of cerebral ischemia.

Animals ; Behavior, Animal ; drug effects ; Brain Edema ; pathology ; Brain Ischemia ; chemically induced ; pathology ; Cerebral Cortex ; pathology ; Cerebral Infarction ; pathology ; Chromones ; pharmacology ; Corpus Striatum ; pathology ; Endothelin-1 ; Leukotriene Antagonists ; pharmacology ; Male ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the molecular mechanism of Wenxin Capsule (WXC, an effective Chinese composite drug) in preventing and treating myocardial ischemia of coronary heart disease.

METHODSRat model of myocardial ischemia was established by subcutaneous multi-point injecting isoproterenol. Effect of WXC on cell apoptosis was observed by transmission electron microscopy and TUNEL method, and its effect on apoptotic related gene Bcl-2 and Fas gene protein expression was observed by immunohistochemical method.

RESULTSIsoproterenol induced myocardial ischemic injury could cause evident cardial cell apoptosis, obvious enhance Fas gene protein expression and mild enhance Bcl-2 gene protein expression. WXC could significantly down-regulate Fas, up-regulate Bcl-2 gene protein expression, significantly inhibit and block the myocardial cell apoptosis.

CONCLUSIONSTo inhibit and block the event of cell apoptosis through regulating Bcl-2 and Fas gene protein expression in ischemic myocardium might be one of the mechanisms of WXT in preventing and treating myocardial ischemic injury of coronary heart disease.

Animals ; Apoptosis ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; pathology ; Myocytes, Cardiac ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; fas Receptor ; biosynthesis ; genetics