[Intervention effects and mechanism of Chinese herbal medicine of supplementing Qi and activating blood circulation on chronic intermittent hypoxia composite insulin resistance ApoE~(-/-) mice model].

This study aims to observe the intervention effects of Chinese herbal medicine of supplementing Qi and activating blood circulation on chronic intermittent hypoxia(CIH) composite insulin resistance(IR) mediated atherosclerosis(AS) mice model,and to observe the mechanism of SREBP-1 c signaling molecule.IR Apo E-/-mice model was induced by high-fat diet combined with STZ injection.Then the mice were treated with hypoxic animal incubator for 8 h per day and 8 weeks to establish a CIH+IR-ApoE-/-mouse model.Model mice were randomly and averagely divided into normoxic control group(NC),model group(CIH) and SREBPs inhibitor group(betulin),atorvastatin group(WM),TCM low-dose group(TCM-L),TCM middle-dose group(TCM-M) and TCM high-dose group(TCM-H) group.Chinese herbal medicine of supplementing Qi and activating blood circulation including ginsenosides combined with ligustrazine(TMP) were used as intervention drugs.The study observed the effect of drugs on IR,serum lipid,inflammation,stress,AS and SREBP-1 c related molecules.The results showed that fasting blood glucose in TCM-H group decreased compared with other experimental groups(P<0.05).HDL-C level in betulin group,WM group,TCM-H group was higher than that in CIH group(P<0.05).LDL-C level in TCM-M group,TCM-H group is lower than that in CIH group(P<0.05).The level of CRP in CIH group was higher than that in other groups(P<0.05).The level of SOD in TCM-H group was higher than that in CIH group(P<0.05).NC group and CIH group showed obvious AS aortic plaque,while betulin group,WM group,TCM-H group showed reduction in AS plaque(P<0.05).For descending aorta,AS plaque in CIH group was multiple and large,while less and smaller in WM group and TCM-H(P<0.05).The expression of SREBP-1 c and FAS in aorta and skeletal muscle in TCM-H group was lower than that in CIH group(P<0.05).In aorta,the expression of TNF-α and CD106(VCAM-1) was lower in TCM-H group than that in CIH group(P<0.05).In aorta,skeletal muscle and liver,the level of p-IRS-1 in TCM-H group was significantly higher than that in CIH group(P<0.05).In aorta and liver,the expression of HIF-1α in TCM-H group was lower than that in CIH group(P<0.05).The study demonstrated that combination ginsenosides with TMP could improve IR and serum lipid level and inhibit inflammation and oxidative stress as well as ultimately alleviate AS to some extent.And the mechanism of its interventional effects might be related to the inhibition of CIH-induced upregulation of SREBP-1 c related molecules.

[Effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway].

This study aims to explore the intervention effect of Chinese medicine of nourishing kidney and clearing liver on intermittent hypoxia(IH) induced injury model of HUVECs through p38MAPK/NF-κB signaling pathway in vitro. HUVECs injury model was induced by modified IH treatment. The effective components of Chinese medicine of nourishing kidney and clearing liver including isochteroside, aucubin and ligustrazine were used as intervention drugs. The optimal compatibility concentration of them was screened in vitro, and then the optimal compatibility concentration was selected as the intervention dose to observe the effect on p38MAPK/NF-κB signaling pathway in IH induced injury model of HUVECs. The results showed that isochnae, aucubin and ligustrazine had the best anti-inflammatory effect at concentration of 0.01 mg•L-1. NF-κB p65 and p-IκB in the nucleus in IH group were significantly higher than those in the normal control(N) group and the other groups. Immunofluorescence staining showed significant translocation of NF-κB p65 nucleus in IH group, and HUVECs adhesion capacity in IH group was increased significantly. As compared with IH group, the expression levels of p-p38MAPK, NF-κB p65 and p-IκB in p38MAPK inhibitor(INH) group and Chinese medicine of nourishing kidney and clearing liver(GDC) group were significantly decreased, and HUVECs adhesion capacity in INH group and GDC group was significantly inhibited as well. The optimal concentration of Chinese medicine of nourishing kidney and clearing liver can inhibit the phosphorylation of p38MAPK, and then inhibit the nuclear translocation and transcription function of NF-κB. This may be the mechanism of the protective effect of Chinese medicine on IH induced injury model of HUVECs.

[Fluctuant hypertension and platelet activation: current situations and control strategies with integrative medicine].

In recent years a huge amount of clinical studies have proved that fluctuant hypertension could aggravate the damage of target organs and increase the incidence of acute cardio-/cerebrovascular events, when compared with stable hypertension [increased mean artery blood pressure (MBP)]. How to prevent and treat fluctuant hypertension and its damage of target organs has become one of the hot and difficult problems in the field of hypertension studies all over the world. Hypertensive patients often suffer from thromboembolic target organ damage. Platelet activation plays a key role in this progress, but its concrete mechanisms have not been clearly clarified. Based on the in-depth discussions on progress of fluctuant hypertension, its relationship with platelet activation and blood stasis syndrome of Chinese medicine (CM) in recent three years, we proposed, under the fluctuant hypertensive state, the prethrombotic state has occurred in the organisms, i.e., a pathological state featured by platelet activation, liable to have vulnerable thrombopoiesis, and accompanied by endothelial dysfunction. Blood stasis syndrome might occupy an important position in CM syndrome typing of fluctuant hypertension. Herbs for activating blood circulation and removing stasis might have an extensive application prospect.

[Analysis of relationships among syndrome, therapeutic treatment, and Chinese herbal medicine in patients with coronary artery disease based on complex networks].

OBJECTIVE: To analyze the relationships among syndrome, therapeutic method and Chinese herbal medicine in patients with coronary artery disease (CAD). METHODS: Using cross-sectional survey, we collected the clinical information of hospitalized CAD patients through individualized Information Acquisition Platform of CAD. The relationships among syndrome, therapeutic treatment and Chinese herbs were excavated by means of complex networks based on theory of correspondence between prescription and syndrome. RESULTS: The fundamental syndrome factors were blood stasis, qi deficiency, phlegm-turbid, yin deficiency, yang deficiency, qi stagnation, and blood deficiency. The therapeutic treatment mainly included activating blood circulation, clearing heat, invigorating qi, resolving turbid and phlegm, nourishing yin, warming yang qi, and dispersing obstruction. These methods constituted an association with major syndrome factors. The major syndrome factors constituted an association with the following Chinese herbal medicines: Huangqi (Radix Astragali Mongolici), Chenpi (Pericarpium Citri Reticulatae), Dihuang (Radix Rehmanniae), Chuanxiong (Rhizoma Chuanxiong), Baizhu (Rhizoma Atractylodis Macrocephalae), Taoren (Semen Persicae), Fuling (Poria), Gancao (Radix Glycyrrhizae), Banxia (Rhizoma Pinelliae), Zexie (Rhizoma Alismatis), Chishao (Radix Paeoniae Rubra), Danggui (Radix Angelicae Sinensis), Danshen (Radix Salviae Miltiorrhizae), Zhiqiao (Fructus Aurantii Submaturus.), Guizhi (Ramulus Cinnamomi) and Maidong (Radix Ophiopogonis Japonici). The efficacy of Chinese berbal medicines constituting association with syndrome factors mainly included alleviating pain, resolving turbid and phlegm, clearing heat, activating blood circulation, invigorating qi, cooling blood, promoting urination, resolving stagnation, removing toxic material, nourishing blood, regulating qi, quieting spirit, invigorating spleen, regulating menstruation, promoting defecation, moistening dryness, and resolving stasis. CONCLUSION: The therapeutic methods for CAD are based on consistency in theory, method, formula and medicines. Therapeutic methods for clearing heat and removing toxical material should be further studied.

[Autophagy in fibrotic and postoperative remnant liver in rat].

OBJECTIVE: To evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver. METHODS: Male Wistar rats were randomly divided into three groups: control group; fibrosis group, which received the solution of CCl4 in oil twice a week for 5 weeks; and hepatectomy group, which underwent 70% hepatectomy. Liver tissues and plasma were harvested 18 hours after the surgery. The rats' general conditions and plasma liver function were observed. Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope. Qualitative analysis of autophagosome was made base on the data from transmission electron microscope. RESULTS: Compared with the control group, plasma total protein and albumin level significantly decreased in the fibrosis group (P < 0.01). Proliferating cell nuclear antigen (PCNA) index was 85%-95% in the fibrosis group. Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group (P < 0.01), while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group (-95%, P < 0.01; -19%, P < 0.05, respectively). PCNA index was 20%-30% in the hepatectomy group. CONCLUSIONS: Autophagy is weakened after fibrosis and hepatectomy, although it differs between these two processes. Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.

[Theoretical thinking on relationship between toxic-stasis pathogenicity and atherosclerotic vulnerable plaque].

Vulnerable plaque rupture is the main cause of acute coronary syndrome (ACS), a representative cardiovascular thrombotic disease. Considering that the Western medical pathogenetic recognition on vulnerable plaque inflammatory reaction and thrombus formation is similar to the etiopathogenesis and clinical characteristics of toxin and stasis as well as the clinical manifestation of toxic-stasis in TCM, the authors believe that it is necessary to expand the previous TCM thinking on taking blood stasis as the main etiopathogenesis for ACS to that ACS is caused by the toxic-stasis induced vulnerable plaque rupture. Therefore to make sense, depending evidence-based medical principle, the relationship between toxic-stasis and vulnerable plaque forming and rupturing, and to form the clinical norm for diagnosis and treatment of toxic-stasis should be helpful for the prevention and control of ACS.

[Effect of assorted use of Chinese drugs for detoxifying and activating blood circulation on serum high sensitive C-reactive protein in apolipoprotein E gene knock-out mice].

OBJECTIVE: To observe the regulatory effect of assorted use of Chinese drugs for detoxifying and activating blood circulation on serum high sensitive C-reactive protein (hs-CRP) in apolipoprotein E gene knock-out [ApoE (-/-)] mice. METHODS: ApoE (-/-) mice of 13-week old were devided into two groups, 12 in Group A fed with common forage and 98 in Group B with high lipid forage. Besides, 12 C57 BL/6J mice, 13-week old, were set as Group C fed with common forage. After being fed for 19 weeks, and the formation of vulnerable plaque had been confirmed in 2 mice of Group B, the other 96 mice were sub-divided into 8 groups, 12 in each group. Except that 0.4 mL normal saline was infused to the Group B1 as well as Group A and C, the other 7 sub-groups of Group B were respectively medicated with various drugs as follows: B2, Polydatin (PD, an extract from giant knotweed rhizome for detoxicating) 26. 6 mg/kg; B3, Xiongshao Capsule (XS, a Chinese herbal preparation for activating blood circulation), 110 mg/kg; B4, PD 53.2 mg/kg + XS 220 mg/kg; B5, PD 26. 6 mg/kg + XS 110 mg/kg; B6, PD 13.3 mg/kg + XS 55 mg/kg; B7, Lovastatin 3.3 mg/kg; and B8, Xuezhikang (XZK, a Chinese patent drug) 0.2 g/kg, all were administered by dissolving in 0.4 mL of distilled water for gastrogavage. The serum contents of hs-CRP were detected, with blood sample drawing from inferior vena cava, using enzyme-linked immunosorbent assay 17 weeks after medication. RESULTS: The hs-CRP level was significantly higher in Group B1 than in Groups A and C (P <0.05, P <0.01). Comparisons between various sub-groups of Group B in hs-CRP content showed that hs-CRP in Group B2, B4 and B7 was lower than that in B1 (P <0.01), hs-CRP in Group B4 was the lowest, and hs-CRP was lower in Group B2 than in Group B3. CONCLUSION: Assorted use of Chinese drugs for detoxifying and activating blood circulation could reduce serum hs-CRP level in ApoE (-/-) mice.

[Combination and transformation of toxin and blood stasis in etiopathogenesis of thrombotic cerebro-cardiovascular diseases].

According to the basic theory of traditional Chinese medicine (TCM), the pathogenetic factors such as platelet activation, adhesion, congregation and thrombosis fall into the category of blood stasis, while the pathological changes such as tissue necrosis, oxidative stress injury and inflammation, etc, are far beyond the etiological category of blood stasis. The toxin or the combination and transformation of toxin and blood stasis of TCM are involved in the pathogenesis of thrombotic cerebro-cardiovascular diseases. It is significant to recognize and stress the combination and transformation of toxin and stasis in pathogenicity so as to enrich TCM etiology and improve TCM clinical efficacy in the treatment of cerebro-cardiovascular and thrombotic diseases.

[Regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of NF-kappaB and MMP-9 in aorta of apolipoprotein E gene knocked-out mice].

OBJECTIVE: To observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) in aorta of apolipoprotein E gene knocked-out (ApoE (-/-)) mice. METHODS: ApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipidemia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-kappaB and MMP-9 in aorta of mice were determined with immunohistochemical assay. RESULTS: Expressions of NF-kappaB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1 - 6 (P < 0.01), and the optimal effect was shown in group B3 (P <0.01). CONCLUSION: Combined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-kappaB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.

[Present status and research train of thoughts in integrative medicine on unstable plaque].

The changing of atherosclerosis (AS) plaque from stable to unstable is closely related to the incidence of cardio-cerebrovascular events. So, to stabilize AS plaque become the hot point of the modern study on prevention and treatment of cardio-cerebrovascular diseases. The formation of AS plaque is a very long and complicated process with the participation of many factors. However, inflammation reaction plays an important role in the formation and rupture of unstable plaque. Traditional Chinese medicine (TCM) shows latent therapeutic advantages in stabilizing AS plaque with its characteristics of multi-way, multi-link, and multi-target point and all-sided treatment as well as its rather milder adverse reactions. The paper gives a comparatively systematic retrospection of study on unstable plaque treated by integrated Chinese and Western medicine conducted in recent years. Combined with the related topics conducted by the authors, they raise the theory of "unstable plaque is induced by toxinduced by toxin and stagnation", and introduce the study on the intervention of unstable plaque by removing toxic substances and activating blood flow. They believe that the explorative study can provide objective experimental and clinical basis for TCM therapeutic method in stabilizing AS plaque.

[Effect of Acupuncture plus Different Frequency Shock-wave Interventions on Pain Reactions and Motor Function in Knee Osteoarthritis Patients].

OBJECTIVE: To observe the clinical effect of acupuncture plus shock-wave (SW) intervention for osteoarthritis (WA), so as to explore its practicability in clinical practice. METHODS: A total of 120 cases of knee OA patients were randomly divided into 4 groups, namely acupuncture (acupunct) + LFSW, acupunct + MFSW, acupunct + HFSW and routine acupunct groups, with 30 cases in each group. Xuehai (SP 10) , Liangqiu (ST 34), Yanglingquan (GB 34), Xiyan (ST 35) and Ashi-point were punctured with filiform needles which were manipulated with uniform reinforcing-reducing techniques for 15-20 min, once every other day for 7 times. In addition, these acupoints were also respectively stimulated with shock waves(10 Hz, 14 Hz and 18 Hz, pressure: 1-4 bar) delivered from a DolorClastEMS therapeutic apparatus for 600 times in 3 acupunct+ SW groups. The patients' pain response changes of the knee-joint were assessed by using visual analog scale (VAS) and the motility was evaluated by using a 0-3 grade scale. RESULTS After 7 times of treatment, the patients' VAS scores and motility scores were significantly decreased in the acupunct+ LFSW, acupunct+ MFSW, acupunct+ HFSW and routine acupunct groups compared with their own basic values before treatment (P < 0.01), and the therapeutic effect of the acupunct+ MFSW group was significantly superior to those of the other 3 groups in reducing both VAS and motility scores (P < 0.05). Correspondingly, the Deqi sensation score of the acupunct+ MFSW group was markedly higher than those of the other 3 groups (P < 0.05). CONCLUSION: Shock wave acu-puncture treatment is effective in relieving OA patients' knee-joint pain and functional activity, and the therapeutic effect of acu- punct + 14 Hz-SW is better, which is closely with Deqi-sensation.

Chronic intermittent hypoxia and hypertension: a review of systemic inflammation and Chinese medicine.

Obstructive sleep apnea syndrome (OSAS) and hypertension commonly coexist. Clinical studies indicate that OSAS plays a key role in increasing the risk of prevalent hypertension. Chronic intermittent hypoxia (CIH) is the core pathological mechanism of OSAS, and has a close relationship with systemic inflammation. Growing evidence shows that CIH and hypertension are strongly related, involving markers or pathways indicative of systemic inflammation, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6, nuclear factor-kappa B, tumor necrosis factor-α, interleukin-8 and p38 mitogen-activated protein kinase (MAPK)-dependent pathways. Oxidative stress also plays an important role in this process, including in the activation of polymorphonuclear neutrophils. However, the pathophysiological and clinical significance of systemic inflammation in CIH and hypertension is not proven. This review article highlights the relationship between CIH and hypertension through systemic inflammation and the current interventions available in Chinese medicine, to offer a background for the future treatment of OSAS-related hypertension with integrative medicine.

Effect of Qingxuan Granule () on blood pressure variability of hypertensive patients with and without obstructive sleep apnea.

OBJECTIVE: To observe the effect of Qingxuan Granule () on blood pressure variability of hypertensive patients with and without obstructive sleep apnea (OSA). METHODS: This study was a stratified, randomized, doubled-blind, placebo-controlled clinical trial. Ninety mild and moderate hypertensive patients with yin deficiency and yang hyperactivity syndrome were enrolled. Each patient received portable sleep monitoring for OSA diagnosis and 24-h ambulatory blood pressure monitoring (ABPM) for blood pressure diagnosis. According to the OSA diagnosis, the hypertensive patients were assigned to two subgroups, one with OSA (group A), the other without OSA (group B); and in each subgroup, the patients were randomly assigned to the treatment group (group A1 or group B1) and control group (group A2 or group B2). All of the patients were treated by Amlodpine Besylate, in addition, Qingxuan Granule was given to the treatment group (group A1 or group B1), and placebo was given to the control group (group A2 or group B2), respectively. After a 2-month treatment, each patient received portable sleep monitoring and 24-h ABPM again, the difference (D-value) of the blood pressure, and OSA index between pre-treatment and post-treatment were analyzed by covariance analysis in a generalized linear model. In this model, D-value was accepted as dependent variable Y, which was affected by treatment method (considered as factor a), the base level of all indices before treatment (considered as factor b), and OSA condition (considered as factor c). RESULTS: The following indices declined more in total treatment groups (groups A1+B1) than in total control groups (groups A2+B2, P a<0.05): 24-h systolic blood pressure (SBP) standard deviation (SD), daytime SBP SD, night time SBP SD, 24-h diastolic blood pressure (DBP) SD, 24-h DBP coefficient variation (CV), daytime DBP SD, night time DBP SD, and heart rate; the following indices declined less in the patients with OSA than those without OSA (P a<0.05): night time SBP, 24-h SBP SD, daytime SBP SD, night time SBP SD, 24-h DBP SD, 24-h DBP CV, daytime DBP SD, night time DBP SD, night time DBP CV, and heart rate; and the following indices increased less in the patients with OSA than those without OSA (P b<0.05): night time SBP fall rate, night time DBP fall rate. No significant difference was found in OSA' indices after taking Qingxuan Granule (P>0.05), with the exception that hypopnea index decreased and hypopnea improved (P<0.05). CONCLUSIONS: For hypertensive patients, Qingxuan Granule could improve the blood pressure variability, and this effect could be weakened by OSA; also Qingxuan Granule could improve hypopnea in OSA patients.

Clinical significance of inflammation factors in acute coronary syndrome from pathogenic toxin.

The inflammation factors and roles of them in acute coronary syndrome (ACS) were explored. The similarity between the theory of pathogenic toxin in Chinese Medicine and the inflammation response theory in ACS was discussed. The exploration of new inflammatory factors may be helpful for Chinese Medicine in the research of ACS.