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

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

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 build a type 2 diabetes mellitus rat model with cardiac ischemia.

METHODSMale Wistar rats were fed high sucrose and high fat diet for four weeks and then injected with streptozoticin (STZ) (40 mg/kg .i.p.). The levels of fasting blood glucose and serum insulin were monitored every week. The body weights of rats were also measured every week. The blood levels of creatine kinase and lactate dehydrogenase (LDH) were measured following the electrocardiograph used BL-410 biological experiment system.

RESULTSThe serum insulin levels of diabetic rats were 4.05 ng/ml after four weeks high sucrose and high fat diet. The fasting blood glucose levels of diabetic rats were 17.9 mmol/L after injection. Compared with normal group, there was obvious change of S-T segment in the electrocardiograph of diabetic group at the fourteenth week. The levels of creatine kinase and lactate dehydrogenase in diabetic group significantly increased in comparison with those in normal group.

CONCLUSIONThe cardiac ischemia of diabetic rats model is suitable for investigating cardiac disease of diabetes mellitus.

Animals ; Creatine Kinase ; blood ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 2 ; chemically induced ; physiopathology ; Diet, High-Fat ; adverse effects ; Dietary Sucrose ; adverse effects ; Disease Models, Animal ; L-Lactate Dehydrogenase ; blood ; Male ; Myocardial Ischemia ; physiopathology ; Rats ; Rats, Wistar ; Streptozocin

OBJECTIVE: To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA). MATERIALS AND METHODS: Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test. RESULTS: There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795). CONCLUSION: The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.
Animals ; *Disease Models, Animal ; Embolization, Therapeutic/*adverse effects ; Enbucrilate/administration & dosage/*toxicity ; Feasibility Studies ; Hindlimb/*blood supply ; Injections, Intra-Arterial ; Ischemia/*chemically induced/diagnosis ; Magnetic Resonance Angiography/*methods ; Male ; Polyvinyl Alcohol/administration & dosage/*toxicity ; Rats ; Rats, Sprague-Dawley ; Tissue Adhesives/administration & dosage/toxicity

Isoproterenol (ISO)-induced myocardial ischemia animal model has been widely applied to the study of myocardial ischemia and evaluation of drug efficacy. Metabolic profiling of endogenous compounds can make a deep insight into biochemical process of the ISO-induced myocardial ischemia rats. Herein, rats were treated with ISO (2 mg x kg(-1)) for 10 days. After the model was established by measuring myocardial histopathology and plasma creatine kinase, GC/TOF-MS was used to determine endogenous metabolites in plasma and cardiac muscle of rats, and pattern recognition was used to process the data. Results showed that the plasma metabolic profiling of ISO-induced myocardial ischemia rats was significantly different from that of the control, and it had the tendency to the normal state after the discontinue of ISO injection. Besides, the cardiac muscle of rats treated with ISO for 10 days and the normal cardiac muscle could also be separated clearly. The potential biomarkers in plasma and cardiac muscle of model rats had homogeneity and their own specialty. Biochemical metabolic pathway analysis indicated that this myocardial ischemia model was involved in the alternation of energy metabolism, saccharometabolism, lipid metabolism, nucleoside metabolism and amino acid metabolism, and in relationship with oxidative stress. These findings revealed that metabonomics may be a promising tool to evaluate myocardial ischemia rat model induced by ISO and could further extend the study of pharmacodynamic action of drugs at the molecular level.
Animals ; Creatine Kinase ; blood ; Energy Metabolism ; Isoproterenol ; Lipid Metabolism ; Male ; Metabolome ; Metabolomics ; methods ; Myocardial Ischemia ; blood ; chemically induced ; metabolism ; Myocardium ; metabolism ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley

This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl2 and FeCl3. The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microgram Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.
Animals ; Brain Ischemia/chemically induced/pathology/therapy ; Cell Differentiation ; Chitosan/*chemistry ; Coordination Complexes/*chemistry/toxicity ; Ferric Compounds/*chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*chemistry/cytology ; Metal Nanoparticles/*chemistry ; Phenotype ; Rabbits

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

OBJECTIVETo investigate the therapeutic effects of Ginkgo biloba extract (EGb) in rats with acute myocardial injury induced by isoproterenol (ISO).

METHODThe rats, induced by Isoproterenol (4 mg x kg(-1) x d(-1), 10 d, sc), were divided into groups: sham, model, metoprolol (10 mg x kg(-1) x d(-1), 13 d, ig), EGb (100 mg x kg(-1) x d(-1), 13 d, ig).

RESULTThe cardiac parameters of the Model group were compromised significantly in both systolic and diastolic function. Improvement in cardiac function by EGb was significant. In model groups, plasma activities of AST, LDH, CK, HBDH, CKMB and ventricular weight index (LV and RV/BW) were elevated significantly. With the treatment with EGb and metoprolol, the enzymes and ventricular weight index were significantly ameliorated.

CONCLUSIONG. biloba extract was beneficial to cardiac performance by improving myocardium enzymes and cardiac function in isoproterenol induced myocardial injury in rats.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; chemistry ; Hemodynamics ; drug effects ; Isoproterenol ; adverse effects ; Male ; Myocardial Ischemia ; chemically induced ; drug therapy ; enzymology ; physiopathology ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley

Terlipressin is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion. Thus, it has a less adverse reaction than vasopressin. We report a case of ischemic skin complication in a cirrhotic patient treated with terlipressin. A 71-year-old man with liver cirrhosis was admitted because of hematemesis and melena. He was commenced on terlipressin at a dose 1 mg every 6 hours for the treatment of varicieal bleeding. After 36 hours of treatment, skin blistering and ecchymosis was noted on the skin of his upper thigh, scrotal area and trunk. We found that terlipressin was a possible cause of ischemic skin complication based on the skin biopsy finding. Terlipressin may induce a complication of the ischemic event. In spite of rarity, special attention needs to paid on the peripheral ischemic complication of terlipressin.
Aged ; Fatal Outcome ; Hematemesis/diagnosis ; Hemorrhage/drug therapy ; Humans ; Ischemia/*chemically induced/*pathology ; Liver Cirrhosis/*complications ; Lysine Vasopressin/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Melena/diagnosis ; Necrosis ; Skin/*blood supply/drug effects/*pathology ; Vasoconstrictor Agents/administration & dosage/*adverse effects/therapeutic use