作者机构：
[Deng, Yi-Hui; Mei, Zhi-Gang] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & We, Changsha, Hunan, Peoples R China.;[Fu, Xian-Yun; Du, Li-Peng; Luo, YN; Feng, Zhi-Tao; Liu, Xiao-Lu; Luo, Ya-Nan; Jiang, Kang; Feng, ZT; Mei, Zhi-Gang] China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved St, Med Coll, Yichang, Hubei, Peoples R China.;[Huang, Ya-Guang] China Three Gorges Univ, Affiliated Renhe Hosp, Yichang, Hubei, Peoples R China.;[Yang, Song-Bai] China Three Gorges Univ, Yichang Hosp Tradit Chinese Med, Clin Med Coll Tradit Chinese Med, Yichang, Hubei, Peoples R China.;[Zhou, Hua-Jun] China Three Gorges Univ, Inst Neurol, Coll Clin Med Sci 1, Yichang, Hubei, Peoples R China.
通讯机构：
[Luo, YN ; Feng, ZT] C;China Three Gorges Univ, Third Grade Pharmacol Lab Chinese Med Approved St, Med Coll, Yichang, Hubei, Peoples R China.
摘要：
Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at "Baihui", "Quchi" and "Zusanli" acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.
摘要：
Objective To investigate the possible mechanism of Zuogui Jiangtang Tongmai Formulae (ZGJTTMF) (左归降糖通脉方) in the treatment of diabetic vascular complications. Methods Thirty rats were randomly divided into the blank group,the Chinese medicine group and the western medicine group,with 10 rats in each group. The Chinese medicine group was intragastrically given ZGJTTMF 36 g/(kg·d) ,and the western medicine group was given nimodipine tablets 18. 35 mg/(kg·d) and gliclazide sustained-release tablets 27. 5 mg/(kg·d) by gavage. The blank group was intragastrically administered with 4 ml of distilled water. Rats were all given once a day for 5 consecutive days to prepare the drug-containing serum. The advanced glycation end products (AGEs) were set to four concentrations of 50,100,200,and 400 mg/L for 12,24,and 48 h. Effects of AGEs on morphological structural changes of rat brain microvascular endothelial cells (BMECs) were observed to screen for optimal intervention concentrations and times. The drug-containing serum of ZGJTTMF was divided into three concentration groups of 2. 5%,5% and 10%. After 24 hours of action on BMECs,the proliferation rate of BMECs was measured to determine the optimal action concentration of serum containing the drug of ZGJTTMF. The BMECs were divided into the blank group,the model group,the Chinese medicine group and the western medicine group. The Chinese medicine group and the western medicine group were respectively added with corresponding drug-containing serum for intervention. The contents of interleukin-1β (IL-1β) ,intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in the supernatant of each group were detected. Results The optimal concentration and time point of AGEs was 200 mg/L for 24 h,and the optimal concentration of Chinese medicine containing serum was 5%. Compared with the blank group,the contents of IL-1β,ICAM-1 and VCAM-1 in the supernatant of the model group were significantly increased (P < 0. 05) . Compared with the model group,IL-1β,ICAM-1 and VCAM- 1 in the Chinese medicine group and the western medicine group were significantly down-regulated (P < 0. 05) . Conclusion ZGJTTMF can down-regulate the expression of IL-1β,ICAM-1 and VCAM-1,thus inhibiting the inflammatory response,which may be one of the mechanisms of its treatment of diabetic vascular complications.
