Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Effects of environmental factors on the distribution of suitable habitats of Ixodes ovatus in China / 中国血吸虫病防治杂志

Objective To identify the environmental factors affecting the distribution of suitable habitats of Ixodes ovatus, and to examine the effects of environmental changes on the distribution of suitable habitats of I. ovatus. Methods Data pertaining to the distribution of I. ovatus in China were captured by literature review. The distribution of suitable habitats of I. ovatus in China was simulated using the maximum entropy model with the environmental variable data and the I. ovatus distribution data. In addition, the potential distribution of suitable habitats of I. ovatus was predicted based on the 2050 and 2070 environmental data. Results The current suitable habitats of I. ovatus cover 3.11 million km2, accounting for 32.28% of the total land area of China, and they are mainly concentrated in southwestern and northwestern China. Among the screened 16 environmental factors, the standard deviation of seasonal variation of temperature, average annual precipitation and altitude were predominant environmental factors affecting the distribution of suitable habitats of I. ovatus, and these three variables contributed 76.5% to the distribution of suitable habitats of I. ovatus in China. The suitable habitats of I. ovatus were predicted to showing a tendency towards expansion to northwestern and northeastern China in 2050 and 2070, and the proportion of highly suitable habitats of I. ovatus was predicted to increase. Conclusions Moderate climate, adequate precipitation and high altitude are favorable for the survival of I. ovatus. Future climate changes may cause expansion of suitable habitats of I. ovatus in China.

Prediction of suitable habitats of Ixodes persulcatus in China / 中国血吸虫病防治杂志

Objective To evaluate the effects of environmental factors the distribution of Ixodes persulcatus, and to predict the future suitable habitats of I. persulcatus in China. Methods The known distribution sites of I. persulcatus in China were captured from national and international published literatures. The effects of 14 environmental factors on the distribution of I. persulcatus were examined using the Jackknife test, including mean annual temperature, mean monthly temperature range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the wet-test quarter, mean temperature of the coldest quarter, annual mean precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, precipitation of the coldest quarter, elevation, slope, aspect and vegetation. The suitable habitats of I. persulcatus were predicted in China using the maximum entropy model and ArcGIS 10.7 software with the environmental factors. Results Currently, the highly suitable habitats of I. persulcatus covered an area of 886 600 km2 in China, which were predominantly located in northeastern China. The environmental factors that contributed more than 10% to the distribution of the suitable habitats of I. persulcatus in China included annual temperature variation range (39.1%), the coldest quarterly precipitation (23.2%), and the annual mean precipitation (11.9%). Based on the maximum entropy model, the suitable habitats of I. persulcatus were predicted to show a shrinking tendency towards northeastern China in 2070. Conclusions The suitable habitat of I. persulcatus strongly correlates with temperature and precipitation, and climate and environmental changes may lead to shrinking of the future suitable habitat of I. persulcatus in China.

Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice / 中国实验方剂学杂志

<b>Objective::To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice. <b>Method::Ninety male ICR mice were randomly divided into normal group, model(DOX) group, DOX+ Qidong Yixin oral liquid group (9.55, 23.88, 47.75 g·kg^-1) and high dose group (47.75 g·kg^-1) with 15 mice in each group. The normal group and model group were given pure water by gavage, and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days. On the seventh day, normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid. Doxorubicin was injected into the abdominal cavity of the other groups (15 mg·kg^-1). After 21 days, the weight and heart weight of mice were weighed and cardiac index was calculated. Serum was taken for the detection of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST). Heart was taken for hematoxylin-eosin (HE) staining, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) in myocardial tissue were detected. The expression of nuclear factor NF-E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot. <b>Result::Compared with normal group, adriamycin could significantly reduce the body weight of mice (<italic>P</italic><0.01), increase the activities of LDH, CK and AST in serum(<italic>P</italic><0.01), and decrease the activities of antioxidant enzymes (<italic>P</italic><0.01). Compared with DOX group, high dose Qidong Yixin oral liquid could significantly increase the weight of mice (<italic>P</italic><0.05, <italic>P</italic><0.01), decrease the level of myocardial three enzymes(<italic>P</italic><0.01), increase the activity of antioxidant enzymes(<italic>P</italic><0.05, <italic>P</italic><0.01), and increase the expression of Nrf2 and HO-1(<italic>P</italic><0.01). <b>Conclusion::Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity. Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.

Therapeutic effect of ramipril and nifedipine on aged patients with hypertensive heart disease and its influence on cardiac function and inflammatory factor level ／ / 心血管康复医学杂志

Objective :To explore therapeutic effect of ramipril tablet and nifedipine controlled release tablet on aged patients with hypertensive heart disease and its influence on cardiac function and inflammatory factor level .Methods :A total of 186 aged patients with hypertensive heart disease were randomly equally divided into ramipril group ,nifedipine group and com‐bined treatment group (received ramipril + nifedipine).After eight weeks ,the therapeutic effect were observed and com‐pared among all groups.Results :Compared with before treatment , there were significant rise in LVEF ,cardiac index (CI) ,left ventricular early diastolic／late diastolic peak flow velocity (E／A) and 6min walking distance (6MWD) ,and sig‐nificant reductions in plasma levels of BNP ,CRP ,interleukin (IL)‐1 and IL‐6 after treatment in three groups , P＜0.01 all.Compared with ramipril group and nifedipine group after treatment ,there were significant rise in LVEF [ (43.44 ± 5.75)%,(43.41 ± 5.73)% vs.(49.89 ± 5.84)%] ,CI [(2.23 ± 0.64) L·min－1 ·m－2 ,(2.28 ± 0.69) L·min－1 ·m－2 vs.(2.87 ± 0.71) L·min－1 ·m－2 ] ,E／A [(0.87 ± 0.31) ,(0.90 ± 0.32) vs.(1.21 ± 0.39)] ,6MWD [(233.44 ± 38.95) m ,(236.45 ± 39.13) m vs.(299.77 ± 45.77) m] ,and significant reductions in plasma levels of BNP [ (199.67 ± 27.86) ng／L ,(194.55 ± 25.46) ng／L vs.(124.67 ± 29.45) ng／L] ,CRP [ (10.32 ± 3.18) mg／L ,(10.21 ± 2.89) mg／L vs. (8.35 ± 2.12) mg／L] , tumor necrosis factor (TNF)‐α [ (45.52 ± 14.56) pg／ml ,(45.45 ± 13.78) pg／ml vs.(37.86 ± 10.35) pg／ml] ,IL‐1 [ (6.34 ± 2.54) pg／ml ,(6.31 ± 2.31) pg／ml vs.(3.42 ± 1.89) pg／ml] and IL‐6 [ (6.71 ± 2.23) pg／ml ,(6.68 ± 2.11) pg／ml vs.(4.11 ± 1.75) pg／ml] , P＝0.001 all.Over all therapeutic effect of combined treatment was significantly higher than that of ramipril group ( Z＝ 3.747 , P＝ 0.001 ) and nifedipine group ( Z＝ 3.838 , P＝0.001).Conclusion :Ramipril combined nifedipine can improve therapeutic effect and cardiac function ,and reduce plasma levels of inflammatory factors in aged patients with hypertensive heart disease .

Protective effects of scutellarin on diabetic cardiomyopathy in mice / 药学学报

To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg∙kg-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen III in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.

Multi-channel in vivo recording technique: microdrive array fabrication and electrode implantation in mice / 生理学报

Here we describe and illustrate our methods for multi-channel in vivo recording in mice, including the fabrication of the microdrive array and the surgical procedure for implanting electrodes. The multi-channel microdrive is fabricated from printed circuit board base, screws, nuts and clamping screws. Rotation of the screw drives both the nut and the attached electrodes to move forward simultaneously. Each full turn of the screw corresponds to 280 µm in depth penetration. The recording electrodes are self-made tetrodes consisting 4 wires (13 µm in diameter). The major steps of headstage fabrication include: tetrode making, microdrive construction, headstage assembling and tetrode plating. The finished headstage is suitable for multi-channel recording in freely moving rodents with the modest weight and the adjustable number of recording electrodes. Additionally, the recording site is allowed to be manipulated after implantation at any time. In the latter part of this paper, we introduce the procedure of the implant surgery to record in bilateral hippocampus in mice. Using these headstages, we simultaneously recorded population activity in bilateral CA1 in freely behaving mice.