The modulation and mechanisms of high-altitude hypoxia in drug transport across the blood-brain barrier / 药学学报

The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury / 中国应用生理学杂志

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

Effect of hypoxia on drug metabolizing enzymes and transporters and the role of microRNA / 药学学报

The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA (miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.

Changes in the intestinal flora of rats under high altitude hypoxia / 药学学报

The structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia was investigated. Animal experiments strictly follow the regulations of Medical Laboratory Animal Ethics Committee of Qinghai University, School of Medicine. SD rats were randomly divided into a control group, a moderate altitude hypoxia group, and a high altitude hypoxia group. The pH value of the feces was measured and histopathological changes in the small intestine were determined by HE staining, and the intestinal flora were characterized by 16S rDNA high throughput sequencing technology on the 3rd, 7th, 15th, and 30th day of hypoxia exposure. Compared with the control group, the fecal pH value of rats in the moderate altitude hypoxia group and the high altitude hypoxia group was decreased significantly. The lamina propria and submucosa capillaries were slightly dilated and congested on the 3rd day in the moderate altitude hypoxia group. In the high altitude hypoxia group the submembrane capillaries were dilated and congested, the lamina propria of the mucosa showed mild edema, and the lymphatic vessels were dilated on the 7th day. The composition and diversity of intestinal flora in these rats changed significantly with prolonged exposure to the high altitude hypoxic environment. A total of 35 phyla, 87 classes, 205 orders, 337 families, 638 genera, and 256 species were annotated in the three groups of rats, including Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Akkermansia, and Lactobacillus_murinus. Compared with the control group, the intestinal flora of the hypoxic groups showed the most significant changes by the 15th day. There were 9 microbiota of gut microorganisms with relative abundance in the moderate altitude hypoxia group, of which Rikenellaceae_RC9_gut_group bacteria was the most common, there were 19 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group, of which Ruminococcaceae bacteria was the most common. The results of this study indicate significant changes in the intestinal flora with high altitude hypoxia, and establish a foundation for further research on the initiation and development of diseases and drug metabolism in high altitude hypoxia.

Endoscopy-assisted internal fixation of ramus and subcondylar fracture / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate clinical application of endoscopy-assisted internal fixation of ramus and subcondylar fractures.</p><p><b>METHODS</b>In 11 patients with mandibular ramus and subcondylar fractures, endoscopy-assisted internal fixations with titanium plates were performed using micro-angular drill and screwdriver.</p><p><b>RESULTS</b>All of the patients showed no visible facial scars. Orthorpantography and three dimensional reconstructions of spiral CT scan demonstrated that all fractures were healed 1 to 15 months after operation. Slight malocclusion existed in 1 case and slight limited mouth openings were found in 2 cases.</p><p><b>CONCLUSIONS</b>Endoscopy-assisted internal fixation of mandibular ramus and subcondylar fracture avoided visible facial scars and the risk of facial nerve damage, it is, therefore, a minimally invasive and effective procedure.</p>

Effects of Chinese herbs on enkephalin mRNA and prodynorphin mRNA gene expression in rat hippocampus with chronic immobilization stress / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of enkephalin mRNA and prodynorphin mRNA gene expression in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.</p><p><b>METHODS</b>We copied the rat model of chronic immobilization stress (3 h daily , repeated 7 d or 21 d), and primers of enkephalin or prodynorphin were respectively added for RT-PCR reaction (BETA-actin as inner contrast). Gel image analysis system was used to scan and analyze and odds of optical density of target gene and inner contrast strip were taken as quasi-quantified data.</p><p><b>RESULTS</b>Prodynorphin mRNA expression in hippocampus markedly increased in 7 d group (P < 0.01), while enkephalin mRNA prodynorphin mRNA expression in hippocampus markedly increased in 21 d group (P < 0.01). All three recipes were able to decrease the gene expression of prodynorphin mRNA (P < 0.01), and xiaoyao powder as well as sijunzi soup were able to decrease the gene expression of enkephalin mRNA (P < 0.01).</p><p><b>CONCLUSION</b>The effects of xiaoyao powder on the above two gene expression was better than jinkuishenqi pill.</p>

Effects of Chinese herbs on glucocorticoid receptor in rat brain regions with chronic immobilization stress / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of glucocorticoid receptor (GR) in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.</p><p><b>METHODS</b>We copied the rat model of chronic immobilization stress (180 min daily, repeated 7 days or 21 days), and characterized the changes of GR in hippocampus CA1, cortex, dentate gyrus via immunohistochemistry integrated image analysis.</p><p><b>RESULTS</b>The contents of glucocorticoid receptors in hippocampus CA1 , cortex, dentate gyrus were increased and the intensity of immunity reaction was significantly stronger in the model group of 7 days than that in the normal control group (P < 0.05). The contents of GR were significantly decreased and the intensity of immunity reaction was weaken in the model group of 21 days (P < 0.05).</p><p><b>CONCLUSION</b>Compared with the model group of 21 days, the contents of GR were significantly increased and immunity reaction was intensified in three groups of treatment with Chinese herbs (P < 0.05), in which the group treated with soothing-liver herbs Xiaoyaopowder was the best.</p>