Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.

Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.

Enriched environment enhanced the astrocyte-derived BDNF and VEGF expression and alleviate white matter injuries of rats with ischemic stroke.

OBJECTIVES: Numerous studies have shown that an enriched environment can promote ischemic stroke and improve cognitive function. In addition, white matter is closely related to cognitive function. The effects and mechanisms of the enriched environment on white matter recovery after stroke have not been elucidated. This study will analyse the effects of the enriched environment on white matter and cognitive function in the post-stroke brain from the perspective of astrocytes and their secretions. METHODS: Stroke models were used for middle cerebral artery occlusion model. post-operative rats were divided into sham-operated, standard and enriched environment groups. The degree of cerebral infarction was assessed by TTC staining and the degree of white matter damage was assessed by Luxol-Fast Blue staining. The prognosis after stroke was assessed using the longa score and Morris water maze test. Western Blot and immunofluorescence were used to quantify and localize astrocytes and their associated secretory factors and myelin protein markers. RESULTS: We found that ischemic stroke can cause severe demyelination. After EE treatment, there was a significant increase in cerebral remyelination and a significant improvement in neurological and cognitive functions. Astrocyte, BDNF, and VEGF expression were significantly higher than in rats in the standard circumstances of stroke model. CONCLUSION: These data suggest that the enriched environment contributes to brain white matter recovery and improvement of cognitive function after stroke. The mechanism is related to astrocytes and their secretions. EE can activate astrocytes to secrete BDNF and VEGF, which may be crucial to promote white matter recovery.

An independent inter- and intra-observer agreement assessment of Yeom classification for bone cement leakage following vertebroplasty/kyphoplasty.

STUDY DESIGN: An inter- and intra-observer agreement study. BACKGROUND: In recent years, vertebroplasty and kyphoplasty have been widely used in treating osteoporotic vertebral compression fractures (OVCF) though the clinical efficacy of them is still controversial. However, there are also inevitable complications, first and foremost is bone cement leakage (BCL). Yeom classification is commonly used to evaluate BCL. The objective of this study is to assess its reliability and reproducibility, and to explore its clinical application value. METHODS: All 58 patients with BCL following vertebroplasty/kyphoplasty were involved. Six spine surgeons were selected to be evaluators as they were unaware of the identity of the patients and the treatment they received. They classified BCL according to Yeom system, we used kappa (K) to assess the inter- and intra-observer agreement. After 12 weeks, we repeated the analysis. RESULTS: The inter-observer reliability of Yeom classification was substantial with K value of 0.71 (1st assessment) and 0.73 (2nd assessment). The intra-observer reproducibility of Yeom classification was near perfect with K value of 0.88. CONCLUSION: Yeom classification system has substantial inter-observer reliability and near perfect intra-observer reproducibility in BCL following vertebroplasty/kyphoplasty, which can be widely used in clinical care as an appropriate instrument for early observation, mechanism and severity cognition, and prognosis predicting of BCL. Besides, the adding of type M (the mixed type) may improve the classification.

The role of enriched environment in neural development and repair.

In addition to genetic information, environmental factors play an important role in the structure and function of nervous system and the occurrence and development of some nervous system diseases. Enriched environment (EE) can not only promote normal neural development through enhancing neuroplasticity but also play a nerve repair role in restoring functional activities during CNS injury by morphological and cellular and molecular adaptations in the brain. Different stages of development after birth respond to the environment to varying degrees. Therefore, we systematically review the pro-developmental and anti-stress value of EE during pregnancy, pre-weaning, and "adolescence" and analyze the difference in the effects of EE and its sub-components, especially with physical exercise. In our exploration of potential mechanisms that promote neurodevelopment, we have found that not all sub-components exert maximum value throughout the developmental phase, such as animals that do not respond to physical activity before weaning, and that EE is not superior to its sub-components in all respects. EE affects the developing and adult brain, resulting in some neuroplastic changes in the microscopic and macroscopic anatomy, finally contributing to enhanced learning and memory capacity. These positive promoting influences are particularly prominent regarding neural repair after neurobiological disorders. Taking cerebral ischemia as an example, we analyzed the molecular mediators of EE promoting repair from various dimensions. We found that EE does not always lead to positive effects on nerve repair, such as infarct size. In view of the classic issues such as standardization and relativity of EE have been thoroughly discussed, we finally focus on analyzing the essentiality of the time window of EE action and clinical translation in order to devote to the future research direction of EE and rapid and reasonable clinical application.

Diagnostic performance of miR-21, miR-124, miR-132, and miR-200b serums in post-stroke cognitive impairment patients.

INTRODUCTION: The diagnosis of post-stroke cognitive impairment (PSCI) mainly depends on neuro-psychological evaluation. It still lacks a sensitive and objective diagnostic biomarker. MicroRNAs (miRNAs, miRs) are novel and potential disease biomarkers. Our aim was to detect which specific miRNA is a good diagnostic biomarker for PSCI. MATERIAL AND METHODS: There were 77 first-ever stroke patients enrolled. Blood samples were collected at 14 days after stroke. Level of serum miR-21, miR-124, miR-132, and miR-200b were determined by quantitative polymerase chain reaction. Mini-mental state examination (MMSE) scale was used to measure the cognitive function of patients. Factional anisotropy (FA) score of diffusion tensor imaging was applied to detect the alteration of white matter. In addition, the relationship between miRNA level and cognitive status was further explored by correlation analysis. RESULTS: Finally, 45 PSCI and 32 post-stroke cognitive normality (PSCN) patients were enrolled. The expression of miR-21, miR-132, and miR-200b in PSCI patients was higher than in PSCN patients. In particular, the miR-21 level was substantially correlated with MMSE scores (r = 0.752, p < 0.001) and FA value (r = 0.636, p < 0.001). Additionally, the diagnostic performance of miR-21 alone or the combination of miR-21 and FA values performed well. CONCLUSIONS: The miR-21 alone or combination of miR-21 and FA values are valuable diagnostic biomarkers in discriminating PSCI from PSCN.

Enriched Environment Effects on Myelination of the Central Nervous System: Role of Glial Cells.

Myelination is regulated by various glial cells in the central nervous system (CNS), including oligodendrocytes (OLs), microglia, and astrocytes. Myelination of the CNS requires the generation of functionally mature OLs from OPCs. OLs are the myelin-forming cells in the CNS. Microglia play both beneficial and detrimental roles during myelin damage and repair. Astrocyte is responsible for myelin formation and regeneration by direct interaction with oligodendrocyte lineage cells. These glial cells are influenced by experience-dependent activities such as environmental enrichment (EE). To date, there are few studies that have investigated the association between EE and glial cells. EE with a complex combination of sensorimotor, cognitive, and social stimulation has a significant effect on cognitive impairment and brain plasticity. Hence, one mechanism through EE improving cognitive function may rely on the mutual effect of EE and glial cells. The purpose of this paper is to review recent research into the efficacy of EE for myelination and glial cells at cellular and molecular levels and offers critical insights for future research directions of EE and the treatment of EE in cognitive impairment disease.

Effects of enriched environment on microglia and functional white matter recovery in rats with post stroke cognitive impairment.

BACKGROUND: White matter damage is an important contributor to cognitive impairment after stroke. This study was designed to explore the beneficial effects of enriched environment (EE) on white matter recovery and cognitive dysfunction after stroke, and further explore the potential mechanism of EE on white matter recovery from the perspective of microglia and microglia-mediated neuroinflammation. METHODS: Male SD rats underwent middle cerebral artery occlusion (MCAO) or sham surgery. During the MCAO operation, a laser Doppler blood flow meter was used to monitor the blood flow to ensure the success of the model. At 72 h after the operation, 3 rats were selected for TTC staining to identify the infarct size. One week after surgery, the rats were randomly assigned into four different groups-MCAO+standard environment (SE), MCAO+enriched environment (EE), Sham+SE and Sham+EE for 4 weeks. At four weeks after MCAO surgery, neurological function deficiency condition and cognitive function were assessed using Longa score and Morris Water Maze prior to euthanasia. The loss or regeneration of myelin was stained with LFB, the expression of myelin regeneration-related protein and microglia protein was quantified by western blot and immunofluorescence, and the level of inflammatory factors was measured by ELISA. RESULTS: EE treatment remarkably decreased the neurological deficit score, ameliorated the cognitive functional deficit in MCAO rats. Furthermore, EE alleviated white matter lesions and demyelination, increased myelin basic protein expression and decreased the number of activated microglia in the hippocampus of MCAO rats. In addition, ELISA analysis indicated that EE decreased the level of IL-1ß, IL-6, which further suggests that EE may reduce the level of pro-inflammatory factors by affecting the expression of microglia marker, IBA1, provide a benefit physiological environment for myelin recovery, and improve post stroke cognitive impairment. CONCLUSIONS: Our results suggest that exposure to EE substantially reduced the damage to brain tissue caused by activation of microglia activation, decreased the level of pro-inflammatory cytokins, which may induced by microglia, protected and promote white matter recovery to improve cognitive function after stroke. Our findings also indicate exposure to EE is beneficial for patients with white matter impairment characterised by white matter disease-related inflammation.

Pre-ischemic exercise prevents inflammation and apoptosis by inhibiting MAPK pathway in ischemic stroke.

Introduction: Mitogen-activated protein kinase (MAPK) pathway is a major mechanism of acute brain damage in ischemic stroke. Pre-ischemic exercise is an effective method to reduce ischemic injury. However, the regulation by pre-ischemic exercise of MAPK pathway and associated mechanisms in animal models remains unclear. Materials and methods: In this study, Male SD rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group, and exercise plus MCAO (EX + MCAO) group for 21 days, and then was established by MCAO. Longa score was used to measure neurological deficits at 0, 1, 2, and 3 days after MCAO. Hematoxylin and eosin staining was used to observe the brain injury. The expression of MAPK pathway was quantified by western blot. The M1 microglia protein was quantified by western blot and immunofluorescence, and the level of inflammatory factor was measured by enzyme-linked immunosorbent assay. TUNEL staining and western blot were used to measure apoptosis. Results: In the current study, we observed that pre-ischemic exercise effectively decreased infarct volume, neurological deficit score and brain injury in MCAO rats through suppressing the activation of p-JNK and p-ERK1/2. Further investigation revealed that pre-ischemic exercise decreased M1 microglia activation and the serum level of TNF-α and IL-1ß. In addition, the increased number of TUNEL-positive cells and Bax/Bcl-2 ratio also were reversed by pre-ischemic exercise. Conclusions: Pre-ischemic exercise can alleviate inflammatory response and apoptosis by inhibiting the MAPK pathway in MCAO rats.

Activation and Role of Astrocytes in Ischemic Stroke.

Ischemic stroke refers to the disorder of blood supply of local brain tissue caused by various reasons. It has high morbidity and mortality worldwide. Astrocytes are the most abundant glial cells in the central nervous system (CNS). They are responsible for the homeostasis, nutrition, and protection of the CNS and play an essential role in many nervous system diseases' physiological and pathological processes. After stroke injury, astrocytes are activated and play a protective role through the heterogeneous and gradual changes of their gene expression, morphology, proliferation, and function, that is, reactive astrocytes. However, the position of reactive astrocytes has always been a controversial topic. Many studies have shown that reactive astrocytes are a double-edged sword with both beneficial and harmful effects. It is worth noting that their different spatial and temporal expression determines astrocytes' various functions. Here, we comprehensively review the different roles and mechanisms of astrocytes after ischemic stroke. In addition, the intracellular mechanism of astrocyte activation has also been involved. More importantly, due to the complex cascade reaction and action mechanism after ischemic stroke, the role of astrocytes is still difficult to define. Still, there is no doubt that astrocytes are one of the critical factors mediating the deterioration or improvement of ischemic stroke.

Mechanism of Endoplasmic Reticulum Stress in Cerebral Ischemia.

Endoplasmic reticulum (ER) is the main organelle for protein synthesis, trafficking and maintaining intracellular Ca2+ homeostasis. The stress response of ER results from the disruption of ER homeostasis in neurological disorders. Among these disorders, cerebral ischemia is a prevalent reason of death and disability in the world. ER stress stemed from ischemic injury initiates unfolded protein response (UPR) regarded as a protection mechanism. Important, disruption of Ca2+ homeostasis resulted from cytosolic Ca2+ overload and depletion of Ca2+ in the lumen of the ER could be a trigger of ER stress and the misfolded protein synthesis. Brain cells including neurons, glial cells and endothelial cells are involved in the complex pathophysiology of ischemic stroke. This is generally important for protein underfolding, but even more for cytosolic Ca2+ overload. Mild ER stress promotes cells to break away from danger signals and enter the adaptive procedure with the activation of pro-survival mechanism to rescue ischemic injury, while chronic ER stress generally serves as a detrimental role on nerve cells via triggering diverse pro-apoptotic mechanism. What's more, the determination of some proteins in UPR during cerebral ischemia to cell fate may have two diametrically opposed results which involves in a specialized set of inflammatory and apoptotic signaling pathways. A reasonable understanding and exploration of the underlying molecular mechanism related to ER stress and cerebral ischemia is a prerequisite for a major breakthrough in stroke treatment in the future. This review focuses on recent findings of the ER stress as well as the progress research of mechanism in ischemic stroke prognosis provide a new treatment idea for recovery of cerebral ischemia.

Limiting potential COVID-19 contagion in squatting public toilets.

BACKGROUND: Since the outbreak of the SARS-CoV-2 virus in December 2019, the COVID-19 pandemic continues to threaten global stability. Transmission of SARS-CoV-2 is mostly by respiratory droplets and direct contact but viral RNA fragments have also been detected in the faecal waste of patients with COVID-19. Cleanliness and effective sanitation of public toilets is a concern, as flushing the toilet is potentially an aerosol generating procedure. When the toilets are of the squatting type and without a cover, there exists a risk of viral contamination through the splashing of toilet water and aerosol generation. OBJECTIVE: This study aims to determine whether the cleanliness of public toilets was a concern to the general population during the COVID-19 pandemic, and whether a squatting toilet was preferred to a seated design. METHODS: A questionnaire was designed and posted on "WeChat" contact groups of the investigators. RESULTS: The survey showed that 91% of participants preferred squatting toilets, but that 72% were apprehensive of personal contamination when using public toilets. Over 63% of the respondents had encountered an incidence of water splash and would prefer public toilets to be covered during flushing and 83% of these respondents preferred a foot-controlled device. CONCLUSION: This survey suggests that consideration should be given to the installation of a simple foot-controlled device to cover public squatting toilets to help restrict potential COVID-19 contamination and to meet hygienic expectations of the public.

Effectiveness and mechanisms of enriched environment in post-stroke cognitive impairment.

Post-stroke cognitive impairment (PSCI) is one of the most common complications of stroke, it is also an important reason for the poor prognosis in stroke patients with motor and speech dysfunction. Enriched Environment (EE), a novel and easy-to-implement rehabilitation treatment strategy, is thought to be a potential intervention for PSCI recently. In this paper, we review the therapeutic effects and related mechanisms of EE in PSCI from the level of animal research and clinical application. Besides, we further discuss the application prospects and limitations of EE in PSCI patients.

Therapeutic Potential of Cytokines in Demyelinating Lesions After Stroke.

White matter damage is a component of most human stroke and usually accounts for at least half of the lesion volume. Subcortical white matter stroke (WMS) accounts for 25% of all strokes and causes severe motor and cognitive dysfunction. The adult brain has a very limited ability to repair white matter damage. Pathological analysis shows that demyelination or myelin loss is the main feature of white matter injury and plays an important role in long-term sensorimotor and cognitive dysfunction. This suggests that demyelination is a major therapeutic target for ischemic stroke injury. An acute inflammatory reaction is triggered by brain ischemia, which is accompanied by cytokine production. The production of cytokines is an important factor affecting demyelination and myelin regeneration. Different cytokines have different effects on myelin damage and myelin regeneration. Exploring the role of cytokines in demyelination and remyelination after stroke and the underlying molecular mechanisms of demyelination and myelin regeneration after ischemic injury is very important for the development of rehabilitation treatment strategies. This review focuses on recent findings on the effects of cytokines on myelin damage and remyelination as well as the progress of research on the role of cytokines in ischemic stroke prognosis to provide a new treatment approach for amelioration of white matter damage after stroke.

The colossal role of H-MnO2-PEG in ischemic stroke.

Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO2 (H-MnO2). The highly monodisperse H-MnO2 with uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study.

Preparation and in vitro and in vivo Study of Asiaticoside-Loaded Nanoemulsions and Nanoemulsions-Based Gels for Transdermal Delivery.

PURPOSE: Asiaticoside (ASI), a compound of triterpene pentacyclic saponins, has apparently therapeutic efficacy on human hypertrophic scar. However, the characteristics of large molecular weight, low water solubility and poor lipophilicity do not favor the diffusion through the stratum corneum (SC). Therefore, it is expected that the development of a transdermally delivered formulation may enhance the permeability ratio (Qn) of ASI for its clinical application. In this study, we designed asiaticoside-loaded nanoemulsions (ASI-NEs) and nanoemulsions-based gels (ASI-NBGs) and studied their mechanism for transdermal delivery. METHODS: The preparation of ASI-NEs was optimized by simplex lattice design (SLD). The ex vivo transdermal penetration and the in vivo pharmacokinetics studies were studied, respectively. The skin irritation of ASI-NEs and ASI-NBGs was measured on normal and damaged skin in rabbits, and the transcutaneous mechanisms of ASI-NEs and ASI-NBGs were determined by HE stained and confocal laser scanning microscopy (CLSM). RESULTS: The mean particle size of ASI-NEs was 132±5.84nm. The ex vivo skin permeation study verified that the Qn of the optimized ASI-NEs and ASI-NBGs was about 13.65 times and 5.05 times higher than that of the ordinary ASI-G group. In vivo, the pharmacokinetics studies showed that ASI-NEs and ASI-NBGs reached the peak value in the skin quickly and maintained stable release for a long time with high bioavailability. ASI-NEs and ASI-NBGs were proved to be safe when applied for topical skin usage, and they could play a therapeutic role through the skin mainly by acting on the microstructure of the SC and by means of the skin adnexal pathways. CONCLUSION: ASI-NEs and ASI-NBGs were effectively developed to overcome the barrier properties of the skin and show high drug penetration through the transdermal route. In addition, we found that ASI-NEs and ASI-NBGs are safe when applied through transdermal delivery system.

Astragalosides increase the cardiac diastolic function and regulate the "Calcium sensing receptor-protein kinase C-protein phosphatase 1" pathway in rats with heart failure.

This study was designed to investigate the effects of astragalosides on cardiac diastolic function, and an emphasis was placed on the variation of the upstream molecular regulators of phospholamban. Chronic heart failure (CHF) rats were induced by ligaturing the left anterior coronary artery, and rats in the therapeutic groups were treated with either a 50 mg/kg dose of captopril, 10 mg/kg dose of astragalosides or 20 mg/kg dose of astragalosides. Four weeks after treatment, the ratio of the early and atrial peak filling velocities (E/A) and maximal slope diastolic pressure decrement (-dp/dt) both decreased in CHF rats (by 30.3% and 25.5%, respectively) and significantly increased in 20 mg/kg astragalosides and captopril-treated rats. The protein phosphatase-1 activity was lower in the 20 mg/kg astragalosides group than in the CHF group (0.22 vs 0.44, P < 0.01), and the inhibitor-1 levels in the astragalosides and captopril-treated groups were increased. Chronic heart failure increased expression of protein kinase C-α and calcium-sensing receptor, and these changes were attenuated by astragalosides therapy. Astragalosides restored the diastolic dysfunction of chronic heart failure rats, possibly by downregulation of calcium-sensing receptor and protein kinase C-α, which in turn augmented inhibitor-1 expression, reduced protein phosphatase-1 activity and increased phospholamban phosphorylation.

[Effects of the Traditional Chinese Medicine berberine on antiatheroscloresis and antioxidant activities in hyperlipoidemic model rats].

OBJECTIVE: To investigate the effects of the Traditional Chinese Medicine berberine on blood lipid and antioxidation ability in hyperlipoidemic model rats. METHODS: Ten rats were randomly chosen as control group, and other rats were used to establish hyperllipemia rat models. Successfully molding rats were randomly divided into model group, berberine low dose group(100 mg/kg), medium dose group(200 mg/kg), high dose group(300 mg/kg), and xuezhikang group(200 mg/kg), 10 rats in each group. Each rat received gavage per day continually for 30 days. Diacylgycerol acyltransferase (DGAT), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), hepatic triglycerides lipase (HTGL), cholesterol 7a-hydroxylase (CYP7A), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high-density lipoprotein (HDL), malondialdehyde (MDA), glutathion peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were monitored. RESULTS: The Traditional Chinese Medicine berberine could obviously decrease the liver coefficient and the contents of TC, TG, LDL-C and increase the serum content of HDL-C in hyperlipoidemia rats. The Traditional Chinese Medicine berberine decrease the levels of MDA, DGAT, HMG-CoA and increase the activities of HTGL, CYP7A, SOD and GSH-Px in liver tissue. CONCLUSIONS: The Traditional Chinese Medicine berberine could decrease the blood lipid level and prevent the lipid peroxidation damage in hyperlidemia rats.

[Modulating effects of shenmai injection on serum lipids in rats with hyperlipemia].

OBJECTIVE: To discuss the modulating effects of shenmai (Traditional Chinese Medicine) injection on blood lipid in hyperlipidemia rats through observing the serum lipid level and a series of related biochemical indexes in hyperlipidemia rat model. METHODS: A total of 30 male SD rats of SPF grade were purchased and fed with basic feed for 1 week to adapt the environment. Then the rats were randomly divided into the following groups(n=10):control group, model control group, shenmai injection group. Control group was fed basal diet; the latter two groups were fed high fat diet,the body weight of all the animals was measured each week. For shenmai injection group, the rats were fed with shenmai injection (10 ml/kg) twice a day for 45 consecutive days through oral administration. The effects of shenmai injection on body weight, serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), super oxide dismutase (SOD), glutathione peroxidase(GSH-Px), malondialdehyde (MDA), the activities of lipoprotein lipase(LPL) and hepatic lipase (HL) in hyperlipidemia rats were detected. RESULTS: Body weight, serum of TC, TG, LDL-C, HDL-C, and MDA levels in model control group were significantly higher(P<0.01), while serum of HDL-C, SOD, GSH-Px, LPL, and HL levels were significantly lower than those of control group(P<0.01). Body weight, serum of TC, TG, LDL-C, HDL-C, and MDA levels in shenmai injection group were significantly lower(P<0.01), while serum of HDL-C, SOD, GSH-Px, LPL, and HL levels were significantly higher than those of model group(P<0.05, P<0.01). CONCLUSIONS: Shenmai injection has a significant effect of modulating blood lipid and antioxidant function on hyperlipidemia rats.

Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide.

Poloxamer 407 has excellent thermo-sensitive gelling properties. Nevertheless, these gels possess inadequate poor bioadhesiveness and high permeability to water, which limited its' application as a thermoresponsive matrix. The main aim of the present investigation was to develop thermosensitive and mucoadhesive rectal in situ gel of nimesulide (NM) by using mucoadhesive polymers such as sodium alginate (Alg-Na) and HPMC. These gels were prepared by addition of mucoadhesive polymers (0.5%) to the formulations of thermosensitive gelling solution containing poloxamer 407 (18%) and nimesulide (2.0%). Polyethylene glycol (PEG) was used to modify gelation temperature and drug release properties. The gelation temperature and drug release rate of the prepared in situ gels were evaluated. Gelation temperature was significantly increased with incorporation of nimesulide (2.0%) in the poloxamer solution, while the addition of the mucoadhesive polymers played a reverse role on gelation temperature. The addition of PEG polymers increased the gelation temperature and the drug release rate. Among the formulations examined, the poloxamer 407/nimesulide/sodium alginate/PEG 4000 (18/2.0/0.5/1.2%) exhibited the appropriate gelation temperature, acceptable drug release rate and rectal retention at the administration site. Furthermore, the micrographic results showed that in situ gel, given at the dose of 20mg/kg, was safe for no mucosa irritation. In addition, it resulted in significantly higher initial serum concentrations, C(max) and AUC of NM compared to the solid suppository.