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

OBJECTIVETo observe the effects of peroxisome proliferator-activated receptor (PPAR) alpha agonist Fenofibrate (FF) on energy metabolism and histology in isoproterenol (Iso) induced acute myocardial ischemic injury model.

METHODSMale Wistar rats were randomly divided into control group, Iso group (5 mg/kg, i.p.) and FF group (80 mgxkg(-1)xd(-1) per gavage for 7 days, then Iso 5 mg/kg, i.p. n = 30 each). Twenty-four hours post Iso, heart weight/body weight ratio, myocardial histopathological changes (HE staining), serum and myocardial free fatty acids (FFA) levels, the myocardial protein expression of PPARalpha (Western blot) were determined.

RESULTCompared with the control group, pathological myocardial injuries were observed under light microscope in Iso treated hearts and FF pretreatment could significantly attenuate these changes [necrotic area: 0 vs (10.00 +/- 3.00)% vs (7.36 +/- 2.60)%], the heart weight/body weight ratio, FFA in serum (501.17 +/- 43.69 vs 939.53 +/- 69.51 vs 736.53 +/- 70.30 micromol/L) and myocardium (62.01 +/- 9.19 vs 140.59 +/- 19.34 vs 116.28 +/- 14.03 micromol/L) were significantly increased while myocardial protein expressions of PPARalpha (251.57 +/- 10.95 vs 191.97 +/- 10.74 vs 215.08 +/- 9.61) was significantly downregulated in the Iso group and FF pretreatment could significantly attenuate these changes (all P < 0.05).

CONCLUSIONOur data suggested that the FFA utilization was decreased in Iso induced acute myocardial ischemic injury and FF could attenuate Iso induced myocardial damage via activating PPARalpha signaling pathway.

Animals ; Disease Models, Animal ; Energy Metabolism ; Fenofibrate ; pharmacology ; therapeutic use ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; prevention & control ; Myocardial Reperfusion Injury ; chemically induced ; metabolism ; prevention & control ; Myocardium ; metabolism ; PPAR alpha ; metabolism ; Rats ; Rats, Wistar

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

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

The hemorrhagic side effects associated with the use of clopidogrel are within the acceptable range and occur mainly at skin or gastrointestinal sites. We report a case of spontaneous spinal epidural hematoma (SSEH) in a 60-yr-old woman who was treated with clopidogrel for frequent transient ischemic attacks. To our knowledge, this is the second reported case of clopidogrel-induced SSEH. The patient's symptoms and past history of clopidogrel use suggested the diagnosis and made the procedure proceed quickly to operate SSEH 9 hr after the onset of paraplegia. The outcome was excellent. Therefore, with the popularity of antiplatelet prescription, physicians should keep in mind and urgently treat this unusual but critical side effect.
Aged ; Brain/pathology ; Cerebral Angiography ; Female ; Hematoma, Epidural, Spinal/*chemically induced ; Humans ; Ischemia/drug therapy ; Magnetic Resonance Imaging ; Platelet Aggregation Inhibitors/*adverse effects ; Ticlopidine/adverse effects/*analogs & derivatives ; Time Factors ; Treatment Outcome

Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing with ornipressin, it is known to have a similar vasoconstricting potency, but much less ischemic complication. We report a case of gangrene on toes and necrosis on the infusion site of left hand which developed after the use of terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver cirrhosis. Ischemic complication of terlipressin is rare and there has been no case report in Korea. Although it is rare, we must pay attention to the peripheral ischemic complication of terlipressin.
Adult ; Hand/*blood supply ; Hepatorenal Syndrome/drug therapy ; Humans ; Ischemia/*chemically induced ; Lysine Vasopressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Toes/*blood supply ; Vasoconstrictor Agents/*adverse effects/therapeutic use