Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.
Brain Ischemia/prevention & control* ; Calcium/metabolism* ; Humans ; Ischemic Stroke ; Mitochondria/pathology* ; Reactive Oxygen Species/metabolism* ; Reperfusion Injury/prevention & control*

Inflammation plays a critical role in intestinal ischemia reperfusion injury (IRI). Epigallocatechin-3-gallate (EGCG) has been demonstrated to possess anti-inflammatory effect. This study examined the effect of EGCG on intestinal IRI and explored the possible mechanisms. Male Wistar rats were randomly divided into three groups: sham-operated group (Sham), IRI control group (IRI) and IRI-EGCG group (EGCG). Rats in IRI-EGCG group were administered dissolved EGCG in drinking water (0.4 mg/mL) for 14 days prior to IRI induction. A rat model of intestinal IRI was established by ligating the superior mesenteric artery (SMA) for 30 min, followed by reperfusion for 1 h. Intestinal histology, pro-inflammatory cytokines and mediators were examined and the effect of EGCG on PI3K/Akt signalling was assessed. EGCG significantly alleviated the pathological changes of the intestine and suppressed the IRI-induced up-regulation of TNF-α, IL-1 and IL-6 mRNA and protein expression in the serum and intestine. The mechanism might be that EGCG enhanced the activation of PI3K/Akt signalling pathway. In conclusion, the administration of EGCG can significantly mitigate the acute intestinal IRI in rats by enhancing the activation of PI3K/Akt signalling pathway to suppress inflammatory response and might be a promising alternative for the prevention or treatment of intestinal IRI in the clinical practice.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; pharmacology ; Catechin ; administration & dosage ; analogs & derivatives ; pharmacology ; Disease Models, Animal ; Gene Expression Regulation ; drug effects ; Interleukin-1 ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Intestines ; drug effects ; pathology ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats.

METHODSEighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope.

RESULTSAt 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A.

CONCLUSIONTadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.

Animals ; Biomarkers ; metabolism ; Carbolines ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Male ; Malondialdehyde ; metabolism ; Phosphodiesterase 5 Inhibitors ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Seminiferous Tubules ; pathology ; Spermatic Cord Torsion ; complications ; Superoxide Dismutase ; metabolism ; Tadalafil ; Testis ; blood supply ; metabolism ; pathology ; Time Factors

OBJECTIVETo study the effects of dopamin receptors-2 (DR2) on myocardial ischemic postconditioning and explore its underlying mechanisms.

METHODSThe myocardial ischemic postconditioning (PC) model was established in cultured primary rat neonatal cardiomyocytes which were then randomly assigned in the following groups: Nomial control group, Isehemia/reperfusion (L'R) group, PC (ischemic postconditioning) group, PC + Bro (Bromocriptine, a DB2 antagonist) group, PC + Hal (Haloperidol, a DB2 repressor) and PC + Hal + Bro groups. The lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed by colorunetry. The cell ultrastructure changes were observed by transmission electron microscope. The cell apoptosis was analyzed using flowcytometiy. The protein expression level of D112 and activity of p-p38 and p-JNK were detected by Western blot.

RESULTSCompared with the nonnal control group, hR increased the protein expression level of DB2, enhanced LDH activity and MDA content, promoted cell injury and apoptosis, decreased SOD activity, up-regulated the activity of p-p38 and p-JNK. Compared with the hR group, although PC further increased the expression of DR2 protein, it decreased LDH activity and MDA content, cell injury and apoptosis, increased SOD activity, down-regulated activity of p-p38 and p-JNK. Bromocriptine treatment further enhanced PC-induced canlioprotective effect, yet Hal addition attenuated this enhancing effect exerted by bromocriptine.

CONCLUSIONThe activation of DB2 is involved in the protective effect of ischemic postconditioning on myocardial ischemia/reperfusion injury through down-regulating the activity of p-p38 and p-JNK.

Animals ; Apoptosis ; Cells, Cultured ; Ischemic Postconditioning ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; pathology ; Rats ; Rats, Wistar ; Receptors, Dopamine D2 ; physiology ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI).

METHODSForty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC).

RESULTSCompared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01).

CONCLUSIONIPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.

Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Disease Models, Animal ; Ischemic Postconditioning ; Lung ; blood supply ; enzymology ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control ; bcl-2-Associated X Protein ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo explore the effect of curcumin (CUR) on cycteinyl aspirate specific protease-12 (Caspase-12) and pneumocyte apoptosis in pulmonary ischemia/reperfusion (I/R) injury mice.

METHODSThe in vivo unilateral in situ pulmonary I/R injury mouse model was established in C57BL/6J mice. Sixty experimental mice were randomly divided into six groups by random digit table, i. e., the sham-operation group (Sham), the I/R group, the I/R + dimethyl sulfoxide group (I/R + DMSO), the I/R + low dose CUR pre-treated group (I/R + CUR-100), the I/R + middle dose CUR pre-treated group (I/R + CUR-150), the I/R + high dose CUR pre-treated group (I/R + CUR-200), 10 in each group. Mice were euthanized and their left lungs were excised. Wet lung weight to dry lung weight (W/D) and the total lung water content (TLW) were tested. The morphological changes of the lung tissue were observed and index of quantitative evaluation for alveolar damage (IQA) detected under light microscope. The ultra-microstructure of the lung tissue was observed under electron microscope. The mRNA and protein expression levels of Caspase-12 and glucose regulated protein (GRP78) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Apoptosis index (AI) of the lung tissue was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method.

RESULTSCompared with the Sham group, expression levels of Caspase-12, GRP78 mRNA and protein all significantly increased in the I/R group (P < 0.05); W/D, TLW, IQA, and AI were all notably higher (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were notably observed in I/R group. Compared with the I/R + DMSO group, expression levels of GRP78 mRNA and protein were increasingly higher in the I/R + CUR-100 group, the I/R + CUR-150 group, and the I/R +CUR-200 group (P < 0.05), expression levels of Caspase-12 mRNA and protein were lower (P < 0.05); W/D, TLW, IQA, and AI also decreased (P < 0.05, P < 0.01); the morphological and ultrastructural injury of the lung tissue were gradually alleviated in the I/R + CUR groups.

CONCLUSIONCUR had better effect on the lung protection against I/R injury, which might be related to inhibition for pneumocyte apoptosis associated with Caspase-12 in excessive unfolded protein response (UPR).

Animals ; Apoptosis ; drug effects ; Caspase 12 ; metabolism ; Curcumin ; pharmacology ; Heat-Shock Proteins ; metabolism ; Lung ; blood supply ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; metabolism ; pathology ; prevention & control

OBJECTIVETo investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism.

METHODSWistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation.

RESULTSLIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury.

CONCLUSIONEndogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema.

Acute Lung Injury ; complications ; pathology ; prevention & control ; Animals ; Aquaporins ; metabolism ; Drug Evaluation, Preclinical ; Edema ; etiology ; pathology ; Hydrogen Sulfide ; pharmacology ; therapeutic use ; Inflammation ; prevention & control ; Lung ; pathology ; Male ; Myeloid Differentiation Factor 88 ; metabolism ; NF-kappa B ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; pathology ; prevention & control ; Toll-Like Receptor 4 ; metabolism ; Water ; metabolism

OBJECTIVETo study the protected effect of Yindan Xinnaotong capsule (YDXNTC) and main components compatibility on myocardium ischemia/reperfusion injury.

METHODGlobal ischemia/reperfusion was adopted to induce myocardial ischemia/reperfusion injury (MIRI) in isolated rat heart. Sprague-Dawley (SD) rats were divided into control, model, YDXNTC, Ginkgo biloba extract (GBE) group, ethanol extract of Salvia miltiorrhiza (SM-E) group, aqueous extract of Salvia miltiorrhiza (SM-H) group, mixed compatibility of other components in YDXNTC (MC), GBE and SM-E compatibility (GSEC), GBE and SM-H compatibility (GSHC), and SM-E and SM-H compatibility (SEHC). During the experiment, electrocardiogram was recorded to observe cardiac arrest time, heart resuscitation time, regaining normal rhythm time, the incidence and duration of arrhythmias (VT/VF). At the end of reperfusion, hearts were arrested and homogenated to assay the activity of superoxide dismutase (SOD), and the content of malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I.

RESULT(1) YDXNTC, SM-E, SM-H and MC elevated cardiac arrest time, also reduced rebeating time, restoring normal rhythm time as well as the duration of arrhythmia, but no remarkable impact on VT/VF occurrence. GBE was effective for incidence of VT/VF, also achieved good effect on shortening rebeating time, restoring normal rhythm time and arrhythmia duration. Likewise, obviously reduced rebeating time, restoring normal rhythm time and arrhythmia duration, and evaluated cardiac arrest time were also exhibited in compatibility groups except that no lengthened cardiac arrest time was detected in GSHC. And the incidence of VT/VF was decreased by GSEC. (2) YDXNT, ginkgo biloba extract (GBE), ethanol extract of salvia miltiorrhiza (SM-E), GBE and SM-E compatibility (GSEC), and SM-E and aqueous extract of salvia miltiorrhiza (SM-H) compatibility (SEHC) could improved SOD and decreased MDA level SM-H, mixed compatibility of other elements in YDXNTC (MC) and GBE and SM-H compatibility (GSHC) showed a role on MDA reduction. (3) LDH was declined by YDXNT and SM-H. CK-MB was reduced by GBE, SM-E, SM-H, and GSEC. (4) The release of cTnI was only inhibited by GSEC.

CONCLUSIONYDXNTC, primary materials and main components compatibility has a certain protection effect on MIRI, its mechanism may be related to antioxidant and calcium overload reduction.

Animals ; Arrhythmias, Cardiac ; physiopathology ; prevention & control ; Capsules ; Creatine Kinase, MB Form ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Electrocardiography ; Ginkgo biloba ; chemistry ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Myocardium ; metabolism ; pathology ; Phytotherapy ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Superoxide Dismutase ; metabolism ; Troponin I ; metabolism

OBJECTIVETo observe the protective effect of Yixinshu capsule on myocardial ischemia reperfusion injury (MIRI) in SD rats.

METHODSixty healthy SD rats were randomized into six groups: sham group, MIRI model group, Xinsuning capsule group, low, middle or high dose Yixinshu capsule. Acute MIRI rat models were created by reperfusion for 120 min after anterior interventricular branch of the left coronary artery for 30 min. The serum creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and malondialdehyde(MDA), blood viscosity, and infarction area of myocardium were determined.

RESULTYixinshu capsule could reduce serum CK, LDH, AST and LDH activity, improve the blood viscosity, and reduced the myocardial infarct size.

CONCLUSIONYixinshu capsule can protect against MIRI in rats.

Animals ; Blood Viscosity ; drug effects ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Lipid Peroxidation ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; pathology ; Myocardial Reperfusion Injury ; prevention & control ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the protective effect of low-dose ketamine against intestinal ischemia reperfusion injury following pneumoperitoneum with carbon dioxide in rats.

METHODSThirty healthy male adult SD rats (body weight 280-320 g) were randomized into sham-operated group, model group and ketamine group and subjected to pneumoperitoneum for 120 min with carbon dioxide (not in sham-operated group). The rats in ketamine group received an intraperitoneal injection of 10 mg/kg ketamine 10 min before pneumoperitoneum, and those in the other two groups received saline injection. Fifteen minutes after pneumoperitoneum or sham operation, the small intestines were sampled to detect the content of malondialdehyde (MDA) and fore pathological testing. ELISA was used to detect the serum levels of I-FABP, TNF-α IL-6 and IL-8.

RESULTSPneumoperitoneum caused a significant increase in intestinal MDA content (P<0.05), which was lowered by ketamine pretreatment (P<0.05). Serum I-FABP, TNF-α, IL-6 and IL-8 levels all significantly increased following pneumoperitoneum (P<0.05) and were obviously lowered by ketamine pretreatment (P<0.05). Pneumoperitoneum also caused obvious pathologies in intestinal mucosa, which were ameliorated by ketamine pretreatment.

CONCLUSIONLow-dose ketamine preconditioning can reduce the inflammatory reaction and lessen oxidative damage in the intestinal mucosa following pneumoperitoneum in rats.

Animals ; Carbon Dioxide ; Dose-Response Relationship, Drug ; Fatty Acid-Binding Proteins ; blood ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Intestine, Small ; blood supply ; metabolism ; pathology ; Ketamine ; administration & dosage ; therapeutic use ; Male ; Malondialdehyde ; metabolism ; Pneumoperitoneum ; chemically induced ; complications ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; etiology ; metabolism ; pathology ; prevention & control ; Tumor Necrosis Factor-alpha ; blood