Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Effect and mechanism of total flavonoids of bugloss on rats with myocardial ischemia and reperfusion injury / 药学学报

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.

Research progress of Bcl-2 regulating autophagy in myocardial ischemia-reperfusion injury / 中国药学杂志

OBJECTIVE: To investigate the relationship between myocardial ischemia-reperfusion injury and Bcl-2 family proteins regulating autophagy were searched, and elaborated the mechanism of Bcl-2 family proteins affecting myocardial ischemia-reperfusion injury by regulating autophagy. METHODS: The literatures which related to myocardial ischemia-reperfusion injury and Bcl-2 family proteins regulating autophagy were searched. The review is finished by analyzing and organizing the literatures. RESULTS AND CONCLUSION: In early ischemia, appropriate autophagy of myocardial cells can reduce the degree of ischemia-induced myocardial injury, however, in the reperfusion period, excessive activation of autophagy can aggravate myocardial cell injury. Bcl-2 family proteins are important regulation factors of autophagy, it can play an important role by interacting with other relevant factors contained in autophagy pathway during the two different periods of myocardial ischemia and reperfusion injury.

Whole brain irradiation for non-small-cell lung cancer with brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the time of whole brain irradiation and the prognostic factors for non-small lung cancer patients with brain metastasis.</p><p><b>METHODS</b>From August 1996 to December 2003, 147 patients with brain metastasis from non-small cell lung cancer received whole brain irradiation. The patients were divided into two groups: with or without symptoms caused by brain metastasis, each group was then divided into two sub-groups, early whole brain irradiation group (the interval between the diagnosis of brain metastasis and the brain irradiation < or = one month) and late group ( the interval > one month ). Univariate and multivariate analysis (Cox regression) as well as Kaplan-Meier method in SPSS software package 11.5 was used to analyze the data of the 147 patients including 72 with brain metastasis symptom and 75 without.</p><p><b>RESULTS</b>The median survival time (MS) of patients with or without extracranial metastasis was 9.9 months and 11.3 months (P = 0.0002). Multivariate analysis indicated that extracranial metastasis was an independent prognostic factor (P = 0.0004). For 72 patients with brain metastasis symptom, the MS of the patients with and without extracranial metastasis was 9.3 months and 11.3 months (P = 0.0036). The MS of patients with early and late whole brain irradiation was 11.4 months and 9.2 months (P = 0.001). Multivariate analysis showed that extracranial metastasis, the interval between the diagnosis of brain metastasis and the whole brain irradiation were independent prognostic factors. However, for 75 patients without brain metastasis symptom, the MS difference of those with early or late whole brain irradiation was not statistically significant (P = 0.1643).</p><p><b>CONCLUSION</b>The extracranial metastasis in non-small cell lung cancer patients with brain metastasis is an independent prognostic factors. Early whole brain irradiation may improve the survival for those with brain metastasis symptoms.</p>