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According to the theory of traditional Chinese medicine, cerebral infarction results from blood stasis, and the method of quickening the blood and dispelling stasis is used to treat cerebral infarct. Salvia Miltorrhiza Bunge (SM) is a Chinese herb, which is considered to have an action of quickening the blood and dispelling stasis, and is frequently used to treat related disorders of blood stasis such as cerebrovascular accident and ischemic heart disease. The aim of the present study was to investigate the effect of SM on cerebral infarct in ischemia-reperfusion injured rats. A total of 30 Sprague-Dawley (SD) rats were studied. A model of focal cerebral infarct was developed by occluding both common carotid arteries and the right middle cerebral artery for 90 minutes. After 24 hours reperfusion, the rats were killed and the brain tissue was stained with 2, 3, 5-triphenyl-tetrazolium chloride (TTC). The areas of cerebral infarct were calculated, and lumino-chemiluminesence (CL) counts and lucigenin-CL counts of peripheral blood taken at this time were measured. The changes in the area of cerebral infarct were used as an index to evaluate the effect of SM on cerebral infarct. The results indicated that pretreatment with intraperitoneal injection of 30 mg/kg and 15 mg/kg SM reduced the area of cerebral infarct and also reduced the luminol-CL counts of peripheral blood in ischemia-reperfusion injured rats. This study has demonstrated that SM can reduce the area of cerebral infarct in ischemia-reperfusion injured rats, suggesting it may be useful in the treatment of cerebral infarct in humans. The therapeutic effect of SM may be partly due to its free radical scavenging activities.

The present study used in vivo rat heart to investigate (1) whether Shen-Fu (SF), a traditional Chinese formulation comprising Radix Ginseng (RG) and Radix Aconitum Carmichaeli (AC), is protective against myocardium damage due to ischemia-reperfusion injury, and (2) whether the cardioprotective effect of SF is related to scavenging of hydroxyl radicals. The model of ischemia-reperfusion injury was established by ligation of left anterior descending coronary artery for 60 minutes followed by reperfusion for 240 minutes in anesthetized rats. The size of infarction and the pathologic changes of myocardium were observed. Lactate dehydrogenase (LDH) and creatine kinase (CK) in serum, the amounts of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were measured at the end of the reperfusion period. Pretreatment groups with SF (10 mg/kg), RG (9 mg/kg) and AC (1 mg/kg) inhibited the rise in MDA and LDH as well as CK, increased SOD activity, reduced the size of infarction, and improved the pathologic changes of myocardium during ischemia-reperfusion compared with the control group. The effect of SF is better than that of RG and AC. These results indicate that SF, RG and AC protect obviously myocardium against damage due to ischemia-reperfusion in rats. The cardioprotective effect of SF injection may be in part related to scavenging of hydroxyl radicals or inhibition of lipid peroxidation. SF is more effective than its separated herbal extracts prepared from RG and AC.

The use of somato-visceral regulation has been proposed as a treatment for a wide range of diseases. The aim of this study was to test the hypothesis that through somato-visceral regulation, ischemia-reperfusion (I/R) injury to the myocardium can be avoided by electroacupuncture (EA) on PC6 (Neiguan).

Electroacupuncture on PC6 (Neiguan) was brought about by the application of metal needles over the bilateral median nerve at a point 1.5 cm proximal to the palm crease in male Spraque-Dawley rats. The animals were randomized into two groups: (1) prevention group with preconditioning by the application of EA on PC6 (n=13); and (2) treatment group with EA on PC6 during I/R injury (n=10). The protection against myocardial injury was blocked by different mechanisms: (1) severing of the bilateral median nerve (n=10), (2) bilateral vagotomy (n=10), and (3) intravenous naloxone injection (n=10). The hemodynamic parameters (mean artery pressure and heart rate), duration of arrhythmia, mortality rate and cardiac enzymes were evaluated in these groups. The results showed that there were significant reductions in cardiac enzymes, the duration of arrhythmia and mortality rate in rats that were either preconditioned or treated with EA on PC6, compared with those that did not undergo EA on PC6 (P<0.05). The cardioprotective effects were blocked by different procedures (P>0.05).

We conclude that EA on bilateral PC6 (Neiguan) prevents and attenuates I/R injury to the heart, and that this approach may provide an applicable and preventative alternative for patients with ischemic heart disease.

Sophora Japonica L. (SJ) is a traditional Chinese herb used to cool blood, stop bleeding and to treat hemorrhoids with bleeding. Although several recent studies found that both SJ and Ginkgo biloba have the same components of quercetin and rutin, only Ginkgo biloba has been widely used to treat cerebrovascular disorders and dementia in humans. This study investigated the effect of SJ on cerebral infarct in rats. A total of 66 Sprague-Dawley (SD) rats were studied. Focal cerebral infarct was established by occluding the bilateral common carotid arteries and the right middle cerebral artery for 90 minutes. After 24 hours of reperfusion, the neurological status was evaluated. The rats were then killed, and brain tissue was stained with 2,3,5-triphenyl-tetrazolium chloride. The grading scale of neurological deficit and the ratio of cerebral infarction area were used as an index to evaluate the effect of SJ on cerebral infarct. In addition, the number of ED1 and interleukin-1β immunostaining positive cells, and apoptotic cells were measured in the cerebral infarction zone. The results indicated that pre-treatment with 100 or 200 mg/kg SJ and post-treatment with 200 mg/kg SJ significantly reduced the grade of neurological deficit and the ratio of cerebral infarction area. In addition, pre-treatment with 200 mg/kg SJ also significantly reduced ED1 and interleukin-1β immunostaining positive cells, and apoptotic cells in ischemia-reperfusion cerebral infarct rats. This study demonstrated that SJ could reduce the cerebral infarction area and neurological deficit induced by ischemia-reperfusion in rats, suggesting its potential as a treatment for cerebral infarct in humans. This effect of SJ involves its suppressive action of microglia, interleukin-1β and apoptosis.

Gap junction communication between astrocytes plays an important role in the brain. The purpose of this study was to investigate the effects of Gingko biloba extract (GBE) on the changes of connexin 43 (Cx43) mRNA and protein expression levels of rat cortex and hippocampus induced by ischemia-reperfusion and astrocyte gap junction intercellular communication (GJIC) induced by hypoxia-reoxygenation. After 2 hours of middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion, there was obvious neurological deficit in rats. Cx43 mRNA and protein expression levels of rat cortex and hippocampus in the ischemia hemisphere were decreased significantly. When GBE at doses of 50 and 100 mg/kg body weight was administrated by p.o. daily for 7 days, the neurological deficit was improved, and lower Cx43 mRNA and protein expression levels induced by ischemia-reperfusion were recovered to normal. The i.p. injection of nimodipine (0.7 mg/kg weight body) also showed improvement on neurological deficit and Cx43 expression levels. Astrocyte GJIC was measured by the fluorescence recovery after photobleaching (FRAP). Hypoxia-reoxygenation induced a significant decrease in GJIC. Pretreatment with GBE (100 mg/l) and nimodipine (1.6 mg/l) significantly prevented the hypoxia-reoxygenation inhibition of GJIC. These results suggest that GBE could exert its neuroprotective effects by improvement of Cx43 expression and GJIC induced by hypoxia/ischemia-reoxygenation/ reperfusion injury.

Intestinal ischemia-reperfusion injury (IIRI) is a life-threatening condition requiring prompt medical intervention. Tetramethylpyrazine (TMP) is a biologically active alkaloid isolated from Ligusticum wallichii. Previously, it was shown that TMP causes vasodilatation and inhibition of platelet aggregation as well as exhibits significant antioxidant effects. Therefore, the aim of the present study was to evaluate possible therapeutic effects of TMP in the prevention of IIRI. Wistar rats (n = 80) were randomly divided into eight experimental groups and subjected to a 1 h occlusion of cranial mesenteric artery followed by 0, 1, 12, and 24 h period of reperfusion. Thirty minutes before the IIRI animals received either TMP (30 mg/kg, i.v.) or identical volume of saline. In addition, a control group of 10 animals was not exposed to IIRI. Intestine morphology was evaluated by using histopathological injury index examination (HII), goblet and Paneth cells quantification as well as by applying immunofluorescent methods such as InSitu TUNEL and caspase-3 positivity assessment. Here we showed that preconditioning with TMP prior IIRI decreases the grade of injury. Significant reduction of HII was detected in TMP pretreated groups after 0, 1, and 12 h of reperfusion where injury reduction up to 75% was found. Lower histopathological damage in preconditioned groups was accompanied with increased number of secretory epithelial cells and decreased number of apoptotic cells. These results demonstrate the protective effect of TMP on the small intestine mucosa, suggesting administration of TMP as a molecule for pharmacological intervention against IIRI.

Berberine (BBR) has been shown to attenuate the deleterious effects of ischemia/reperfusion (I/R) injury in the brain. We evaluated the effects of BBR on intestinal tight junction (TJ) changes during mesenteric I/R. I/R was induced in rats by the occlusion of the superior mesenteric artery and reperfusion. The rats were randomized into four groups: control, BBR, I/R, and I/R + BBR. Intestinal permeability was determined by the lactulose/mannitol test. The ileum and colon were harvested to assess mucosal injury and inducible nitric oxide synthase activity. The TJ ultrastructure was studied by transmission electron microscopy. The expressions and locations of the TJ proteins, occludin and ZO-1, in the epithelium were investigated by immunofluorescence microscopy. We also used Western blot analysis to detect the distribution of TJ proteins in lipid raft fractions. Our results suggest that I/R-induced intestinal TJ dysfunction can be improved by BBR, thereby demonstrating the therapeutic potential of BBR for intestinal I/R.

Objective: To explore the early expression of autophagy-associated proteins in lung tissues in acute lung injury (ALI) induced by remote limb ischemia-reperfusion (LIR) by using rats as our test specimens. Method: A total of 48 adult male Sprague-Dawley (SD) rats with weights in the range of 220–250g were designated as LIR models, and divided randomly into two groups of 24 each: Sham group and ischemia-reperfusion (I/R) group. Then, each group was divided into four subgroups at the end of 0, 2, 4, 8h of reperfusion, after 3h of ischemia. The rats were anesthetized by pentobarbital sodium. The serum lactate dehydrogenases (LDH) were detected with enzyme linked immunosorbent assay (ELISA), and the pathological changes of lung tissues were observed by using immunofluorescence techniques. The expression of Beclin1 protein and Atg5 mRNA in the lung tissues were detected by using reverse transcription polymerase chain reaction (RT-PCR), and analyzed by 2${}^{-\mathrm{\Delta }\mathrm{\Delta }\mathrm{\text{CT}}}$ method; Microtubules associated protein light chain 3 (LC3) in the lung tissues were detected by Western blot test. Result: The levels of serum LDH in I/R groups were much higher than those in Sham groups ($P<0.01$), which showed that the rats models of LIR were successful. Immunofluorescence examination demonstrated injuries of lung tissues, thickening of alveolar septum and partial consolidation in I/R groups; however, this damage was not observed significantly in Sham groups. The expression of Beclin1 and Atg5 mRNA, LC3-II and the ratio of LC3-II/GAPDH in lung tissues were very much higher at 4 and 8h in IR groups ($P<0.01$ or $P<0.05$), and were significantly higher at the same time compared with Sham groups ($P<0.01$ or $P<0.05$). Conclusion: LIR causes ALI to induce increased autophagy and high expression of its relevant proteins; while continuous I/R can also cause autophagy inhibition.