Dexmedetomidine inhibits abnormal muscle hypertrophy of myofascial trigger points via TNF-α/ NF-κB signaling pathway in rats.

Myofascial pain syndrome (MPS) is a chronic pain disorder with inflammation-related primarily characterized by the presence of myofascial trigger points (MTrPs). Myocyte enhancer factor 2C (MEF2C) is involved in the occurrence of a variety of skeletal muscle diseases. However, it is not yet clear if MEF2C is involved in MTrPs. The purpose of this study was to investigate whether MEF2C was involved in the inflammatory pathogenesis of MTrPs. In the present study, we used RNA sequencing (RNA-seq) to compare the differential expression of myocyte enhancer factor 2C (MEF2C) in healthy participants and MTrPs participants. The widely used rat MTrPs model was established to research the upstream and downstream regulatory mechanism of MEF2C and found that MEF2C was significantly increased in patients with MTrPs. Dexmedetomidine (Dex) was injected intramuscularly in the MTrPs animal to assess its effects on MEF2C. The expression of MEF2C protein and mRNA in skeletal muscle of rats in the MTrPs group were up-regulated. In addition, the expression of TNF- α, p-P65, MLCK, and Myocilin (MyoC) was up-regulated and the mechanical pain threshold was decreased. Peripheral TNF- α injection significantly decreased the mechanical pain threshold and increased the expression of p-P65, MLCK, MEF2C, and MyoC in healthy rats. Maslinic acid increased the mechanical pain threshold and inhibited the expression of p-P65, MLCK, MEF2C, and MyoC. In addition, peripheral injection of DEX in MTrPs rats also inhibited the expression of TNF- α, p-P65, MLCK, MEF2C, and MyoC. These results suggest that MEF2C is involved in the inflammatory pathogenesis of MTrPs and DEX serves as a potential therapeutic strategy for the treatment of MPS.

Learning and memory ability and its mechanism in rats with focal cerebral ischemia induced by two filament-occluded methods / 中国康复理论与实践

ObjectiveTo explore the difference of learning and memory function between permanent cerebral ischemia and ischemia-reperfusion rat models by filament-occluded method after three weeks of natural recovery, and to observe the changes of brain structure. MethodsA total of 21 SPF male Sprague-Dawley rats were randomly divided into sham group (n = 7), permanent ischemia group (n = 7) and ischemia-reperfusion group (n = 7). The latter two group underwent left middle cerebral artery occlusion, and the ischemia-reperfusion group was reperfused after 90 minutes of ischemia. All the rats were tested with Morris Water Maze 16 to 22 days after modeling, to record escape latency in the navigation experiment, as well as first latency, platform quadrant swimming time ratio and distance ratio, boundary swimming time ratio and distance ratio, average speed, and the swimming path in the space exploration experiment. On the 22nd day after modeling, four rats with similar Longa scores in each group were scanned by magnetic resonance by diffusion tensor imaging, to measure the fractional anisotropy (FA) of cerebral ischemic cortex, striatum, hippocampus and their corresponding contralateral regions, to calculate ratio of FA (rFA); as well as the volume of infarct (VI) and ratio of VI (rVI). ResultsFor navigation experiment, the escape latency decreased in all the groups with the time (F = 36.202, P < 0.001), but it was not significant for the permanent ischemia group (F = 4.004, P > 0.05). The escape latency was longer in the permanent ischemia group than in the other two groups at each time points (P < 0.05). For space exploration experiment, the boundary time ratio and distance ratio were more in the permanent ischemia group and the ischemia-reperfusion group than in the sham group (P < 0.017), and the first latency was longer in the permanent ischemia group than in the sham group (P < 0.017). The swimming path of ischemia-reperfusion group and sham operation group was better than that of the permanent ischemia group. FA and rFA in left cortex and striatum were less in the permanent ischemia group and the ischemia-reperfusion group than in the sham group (P < 0.05), while FA and rFA of left cortex and FA of left striatum were less in the permanent ischemia group than in the ischemia-reperfusion group (P < 0.05). The VI and rVI were larger in the permanent ischemia group than in the ischemia-reperfusion group (t > 4.185, P < 0.01). FA and rFA of left cortex and striatum correlated with escape latency, boundary time ratio and distance ratio (|r| > 0.498, P < 0.05). The VI and rVI correlated with escape latency and boundary time ratio (|r| > 0.538, P < 0.05). ConclusionCognitive impairment is more severe in the rat model of permanent cerebral ischemia, which may relate to the larger damage of structure of nerve fibers in ischemic cortex and striatum, and larger infarct size.

Comparison of cardiac function between left bundle branch pacing and right ventricular outflow tract septal pacing in the short-term: A registered controlled clinical trial.

BACKGROUND: The novel method of left bundle branch pacing (LBBP) has been reported to produce a narrower QRS duration and lower pacing threshold than right ventricular outflow tract septal pacing (RVOP). However, whether LBBP is superior to traditional RVOP in improving cardiac function still lacks sufficient evidence. OBJECTIVE: The purpose of this study was to compare the changes in cardiac function (especially in brain natriuretic peptide (BNP)levels, left atrial function, and left ventricular diastolic function) within 7 days between LBBP and RVOP. METHODS AND RESULTS: A single-centre prospective controlled registered clinical study was conducted with 84 patients with bradycardia indications. Forty-two patients underwent RVOP, and 42 patients underwent LBBP. The pacemaker parameters were adjusted so that the ventricular ratio was over 90% and rate was 60-70 bpm. The changes in BNP levels and echocardiogram and speckle-tracking echocardiagraphy findings were compared between the two groups before and within 7 days after implantation: (1) BNP: there was no significant difference in BNP level between the two groups before and 1 day after implantation, while the LBBP group had significantly lower levels than the RVOP group on day 7 [(65.15 ± 56.96)pg/ml vs.(129.82 ± 101.92)pg/ml, P < 0.001]. (2) Cardiac echocardiography: the e' value of the LBBP group was higher than that of the RVOP group 7 days after implantation[(6.39 ± 2.65) cm/s vs. (5.45 ± 1.35)cm/s, P = 0.049]. The E/e' and peak E-wave velocity in the LBBP group decreased significantly after 7 days [16.57 ± 6.55 vs. 12.75 ± 5.16 P = 0.043, (88.6 ± 24.37)cm/s vs. (75.68 ± 28.10)cm/s P = 0.030]; in contrast, there were no significant changes in the RVOP group [14.13 ± 3.85 vs.14.10 ± 4.85 P = 0.50, (77.33 ± 21.14)cm/s vs. (74.45 ± 23.03)cm/s P = 0.56). (3)Speckle-tracking echocardiagraphy: there was no significant difference in left atrial strain or the strain rate between the LBBP and RVOP groups，but the absolute values of left atrial strain and strain rate in the LBBP group increased, while those in the RVOP group decreased. CONCLUSION: This study demonstrates that compared to RVOP, LBBP can increase left ventricular early diastolic function, improve BNP levels, and has a tendency to increase left atrial myocardial elasticity and left atrial strain capacity in the short term in pacemaker-dependent patients.

Mild Mechanic Stimulate on Acupoints Regulation of CGRP-Positive Cells and Microglia Morphology in Spinal Cord of Sciatic Nerve Injured Rats.

OBJECTIVE: The objective of this study is to observe the effects of mild mechanical stimulation on acupuncture points of spinal motor neurons and active substances of sciatic nerve injury in rats, and to explore the morphological basis for the recovery of motor function in rats with sciatic nerve injury, using mild acupuncture. Acupuncture in the local area of injury may cause further damage to the peripheral nerve injury. We believe that mild mechanical stimulation on the surface, using some specific acupuncture points can also have a positive effect on nerve repair. This method, called Chinese tuina, has existed for more than 2,000 years in China. METHODS: This study establishes a rat model using sciatic nerve crush injury. Rats received Chinese tuina in accordance with the principle of the three methods and three points, once a day, for 20 days. The rats' status of hindlimb recovery was detected by a sciatic functional index. The labeled neuronal cell body was used to evaluate the fiber recovery after the rats' sciatic nerve injury, using a neural tracing technique. Our team studied motor neuronal cell bodies, CGRP-positive cells, and the microglia of damaged sciatic nerves which were stained with fluorescent triple staining, adopting a confocal multi-layer scanning technique, and then the changes in neuronal activity distribution and expression, and changes of time and treatment were described, using the method of morphological description. RESULTS: Sciatic nerve injury decreased the survival rate of motor neurons, affected CGRP-positive cells, and activated microglia in the ventral horn of the spinal cord. Compared with the model group, the survival of spinal ventral horn motor neurons was increased through tuina intervention. The swelling of CGRP-positive cells was alleviated, and the degree of microglia activation was less than that of the model group. CONCLUSION: This study used visual morphological findings to assess changes in neurons and active substances with time after injury of the peripheral nerve, and demonstrated that peripheral mild acupuncture intervention improved the capacity of neurofibrillary axoplasmic transport, regulated microglia activation, and significantly promoted the recovery of sciatic nerve injury.

Graphene reinforced multiple monolithic fiber solid-phase microextraction of phenoxyacetic acid herbicides in complex samples.

To increase the specific surface area (SSA) of monolith-based adsorbent for the extraction of phenoxyacetic acid herbicides (PAAs) in complex samples, graphene was embedded in an adsorbent based on poly (4-vinylpyridine-co-ethylene glycol dimethacrylate) monolith (GEM). The new adsorbent was employed as extraction phase of multiple monolithic fiber solid-phase microextraction (MMF-SPME). The influences of preparation conditions and extraction parameters on the enrichment performance of GEM/MMF-SPME for PAAs were investigated in detail. Results well indicated that the embedded graphene could obviously enhance the SSA of the adsorbent and introduce π-π electrostatic stacking groups. The prepared GEM/MMF-SPME could extract PAAs effectively by means of π-π electrostatic stacking, hydrophobic, ion-exchange and hydrogen bonding interactions. Under the most favorable conditions, a convenient, sensitive, cost-effective and environmentally friendly method for the determination of trace PAAs in water and rice samples was developed by the combination of GEM/MMF-SPME and high performance liquid chromatography-diode array detection (HPLC-DAD). Results showed that for water sample, the limits of detection (LOD, S/N = 3) and limit of quantification (LOQ, S/N = 10) values were in the range of 0.093-0.12 µg/L and 0.31-0.41 µg/L, respectively. The corresponding values in rice sample were 0.36-0.66 µg/kg and 1.18-2.27 µg/kg, respectively. The proposed method was successfully applied to quantify trace PAAs in water and rice samples. Recoveries achieved for water and rice samples at different spiked concentrations were in the ranges of 70.0-118% and 70.0-117%, respectively. The RSDs varied from 0.3% to 10% for all analytes. The results well revealed the potential application of GEM/MMF-SPME as an effective sample preparation processes for the monitoring of PAAs in water, rice and other complex samples.

Clinical and fundamental research Yinhua Miyanling Tablets in treating urinary tract infection / 中国中药杂志

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.

Solid-phase microextraction of sulfonylurea herbicides by using borate-reinforced multiple monolithic fibers.

Boron-nitrogen coordination is a useful interaction for use in the extraction of amino-nitrogen-containing compounds. A new monolithic adsorbent is described here that consisted of poly(acrylamidophenyl boronic acid/vinyl-3-octylimidazolium tetrafluroborate-co-divinylbenzene/ethylene dimethacrylate) polymer. It was synthesized with the aim to obtain a new kind of extraction phase for multiple monolith based fiber solid-phase microextraction of sulfonylurea herbicides. Results indicate that boron-nitrogen coordination interaction plays a key role in the efficient extraction. It is also found that soaking the sorbent in a borate solution further improves the enrichment performance. The preparation conditions and extraction parameters were optimized. Following extraction with the adsorbent, the sulfonylurea herbicides were submitted to quantitation by HPLC with DAD detection. The limits of detection are in the range of 9.0-18 ng·L-1. The method was applied to monitor the herbicides in samples of tap, river and waste waters. Recoveries at spiking levels of 1.0, 10 and 100 µg·L-1 are in the range of 70.1-108%, and the values for relative standard deviation are less than 10% for all analytes in all cases. Graphical abstract Schematic of the monolith-based adsorbent (MBA) on a multiple monolith based fiber (MMF) for use in solid-phase microextraction of sulfonylurea herbicides (SUs).

Mixed functional monomers-based monolithic adsorbent for the effective extraction of sulfonylurea herbicides in water and soil samples.

Effective extraction is a key step in the determination of sulfonylurea herbicides (SUHs) in complicated samples. According to the chemical properties of SUHs, a new monolithic adsorbent utilizing acrylamidophenylboronic acid and vinylimidazole as mixed functional monomers was synthesized. The new adsorbent was employed as the extraction phase of multiple monolithic fiber solid-phase microextraction (MMF-SPME) of SUHs, and the extracted SUHs were determined by high-performance liquid chromatography with diode array detection (HPLC-DAD). Results well evidence that the prepared adsorbent could extract SUHs in environmental waters and soil effectively through multiply interactions such as boronate affinity, dipole-dipole and π-π interactions. Under the optimized extraction conditions, the limits of detection for target SUHs in environmental water and soil samples were 0.018-0.17µg/L and 0.14-1.23µg/kg, respectively. At the same time, the developed method also displayed some analytical merits including wide linear dynamic ranges, good method reproducibility, satisfactory sensitivity and low consume of organic solvent. Finally, the developed were successfully applied to monitor trace SUHs in environmental water and soil samples. The recoveries at three fortified concentrations were in the range of 70.6-119% with RSD below 11% in all cases. The obtained results well demonstrate the excellent practical applicability of the developed MMF-SPME-HPLC-DAD method for the monitoring of SUHs in water and soil samples.

Clinical application evaluation of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection / 中国中药杂志

A questionnaire survey of 1 000 clinicians having experience in treating uncomplicated lower urinary tract infections from different levels of hospitals was conducted to mainly evaluate the applicability and effectiveness of clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection(hereinafter referred to as Guideline). The research was conducted with the three-level quality control strictly throughout the process, and the data was real and reliable. The survey's results showed that: most clinicians considered that the Guideline had good clinical applicability. The availability and price of the recommended medicine were moderate. Traditional Chinese medicine had obvious features and advantages in treating lower urinary tract infection for it could reduce the usage of antibiotics and shorten the course of antibiotic application. In the recommendation section, clinicians proposed increasing medication guidance, updating the Guideline timely, as well as increasing treating methods and techniques, strengthen propaganda and promotion, and improve the use of evidence-based methods. In the evaluation of effectiveness, the majority of clinicians agreed that the definition in both traditional Chinese medicine (TCM) and Western medicine and differential diagnosis in the Guideline were accurately described and the basic principle of treatment as well as the treating method of TCM were recommended appropriately. The TCM formulas and Chinese patent medicine had good effect. Some clinicians suggested refining the syndrome differentiation of stranguria. Some clinicians considered that the formulas and herbs recommended in Guideline didn't have obvious effect and some had doubts about the manipulation of fumigation and washing in the part of other methods recommended in Guideline. Moreover, specification and procedure of manipulation of fumigation and washing using herbs and the acupuncture included in characteristic TCM therapy treating uncomplicated lower urinary tract infection remained to be developed.

Preparation and evaluation of an adsorbent based on poly (muconic acid-co-divinylbenzene/ethylenedimethacrylate) for multiple monolithic fiber solid-phase microextraction of tetracycline antibiotics.

To extract tetracycline antibiotics (TAs) effectively, a new adsorbent based on poly (muconic acid-co-divinylbenzene/ethylenedimethacrylate) monolith was fabricated and used as the extraction medium of multiple monolithic fiber solid-phase microextraction (MD/MF-SPME). The effect of the fabrication parameters on extraction efficiency was studied thoroughly. Elemental analysis, infrared spectroscopy, scanning electron microscopy and mercury intrusion porosimetry were used to check the physicochemical properties of the adsorbent. Some key parameters that affect the extraction performance of MD/MF-SPME for TAs were investigated systematically. Under the optimized experimental conditions, the prepared adsorbent could effectively extract the TAs through multiple interactions. At the same time, a simple and sensitive method for monitoring trace TAs in honey samples was developed by coupling MD/MF-SPME with high-performance liquid chromatography tandem mass spectrometry detection (MD/MF-SPME-HPLC-MS/MS). The limits of detection (S/N=3) for target compounds were in the range of 7.3-17.1ng/kg. The intra-day and inter-day precision (relative standard deviations, n=4, %) at 0.5µg/kg and 20.0µg/kg spiking concentrations were 5.0-9.5% and 3.6-10.0%, respectively. The mean recoveries of the target TAs in the real honey samples were between 70.5-111.0%.

Fabrication of a polymeric ionic liquid-based adsorbent for multiple monolithic fiber solid-phase microextraction of endocrine disrupting chemicals in complicated samples.

A multiple monolithic fiber solid-phase microextraction (MMF-SPME) utilizing polymeric ionic liquid-based adsorbent was prepared. The adsorbent was obtained by in situ copolymerization of an ionic liquid, 1-trimethyl-(4-vinylbenzyl) aminium chloride and dual cross-linkers (divinylbenzene and ethylenedimethacrylate). The effect of preparation conditions including the content of ionic liquid and porogen in the polymerization mixture on extraction performance was studied in detail. Infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry were used to inspect the physicochemical properties of the new adsorbent. The applicability of the new MMF-SPME was demonstrated by the extraction of trace endocrine disrupting chemicals (EDCs). Results indicated that the prepared MMF-SPME could extract EDCs effectively through multi-interactions such as ion-exchange, π-π and hydrophobic interactions. After optimization of extraction parameters, a method of MMF-SPME coupled to high performance liquid chromatography/diode array detection was conducted to detect trace EDCs in complicated samples including environmental water and human urine. The limits of detection (S/N=3) and quantification (S/N=10) for targeted compounds were 0.011-0.065µg/L and 0.036-0.21µg/L, respectively. Satisfactory precision was also achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSDs) of less than 9% and 10%, respectively. At the same time, the proposed method was successfully applied for the determination of EDCs in water and human urine with spiking recoveries ranged from 70.6% to 119%.

Review on advantages and evidence of treating and preventing urinary tract infection in traditional Chinese medicine / 中国中药杂志

Urinary tract infection (UTI) in traditional Chinese medicine (TCM) belongs to the category of stranguria. This article describes the unsatisfactory situations in clinical practice such as antibiotics abuse, increasing of drug-resistant bacteria, high recurrence rate, etc. According to evidence-based medicine, literatures as evidence are collected for summarizing and analyzing and the result shows the advantages of TCM of relieving symptoms, reducing the dosage of antibiotics, less side effects, lower recurrence rate, etc. In the field of fundamental research, literatures associated with UTI are also summarized and analysed from several perspectives, such as causes, pathogenesis, syndrome differentiation, pharmacological effects of Chinese herbal medicine, working mechanism of non-drug therapy, etc and the result presents that integrated treatment of TCM in UTI has significant advangtages and its own characteristic.

Inhibitory effect of different species of hydroxygenkwanin on UGTs and UGT1A1 activities / 中国中药杂志

To predit the mechanism of metabolic drug-drug interactions of hydroxygenkwanin with other drugs, we investigated the inhibition inhibitory effect of hydroxygenkwanin on UGTs and UGT1A1 activities of different liver microsomes. In the present study, 4-nitrophenol (4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. The results showed that, hydroxygenkwanin significantly inhibited UGTs activity in rat, mouse and human liver microsomes. UGT1A1 activity was inhibited by hydroxygenkwanin to varying degrees, with IC₅₀ about 190, 10.93, 20.07, 76.31 μmol•L⁻¹ in mouse liver microsome(MLM), rat liver microsome (RLM) and recombinant UGT1A1, and human liver microsome (HLM), respectively. The inhibition types were competitive inhibition (RLM, HLM) and linear mixed-typed linear inhibition (recombinant UGT1A1). The order for the inhibitory intensity was RLM>rUGT1A1>HLM>MLM. In conclusion, hydroxygenkwanin has an inhibitory effect on UGTs and UGT1A1 activities of different liver microsomes, with differences in species, indicating its potential drug interactions based on UGT1A1 enzyme. This study aims to provide a reliable experimental basis for its further research and development of hydroxygenkwanin, and provide theoretical reference for the clinic drug combination research.

Effects of Early Exercise on Motor Function and Diffusion Tensor Imaging in Rats after Focal Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effects of early exercise on motor function and the mechanism in rats after focal cerebral ischemia. Methods 21 Sprague-Dawley male rats were divided into control group (n=7), natural recovery group (n=7) and exercise training group (n=7), and the latter 2 groups were modeled with middle cerebral artery occlusion. The exercise training group received wheel running exercise 24 hours after modeling for 14 days. They were assessed with Rogers score and beam balance test 21 days after modeling. 4 rats in each group received routine MRI and diffusion tensor imaging (DTI) scanning. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of ischemic (L) and contralateral side (R) were measured, and the rate of them (L/R, r) was calculated. Results There was significant difference in Rogers score among the groups (Z=-0.786, P0.05). Beam balance score of the natural recovery group was significantly different from the control group and the exercise training group (F=38.11, P0.05). The LFA of the natural recovery group was significantly different from the control group (P0.05);while the rFA of the natural recovery group was significantly different from the control group and the exercise training group (F=19.30, P0.05). LFA and rFA strongly correlated with all the behavior scores (r=-0.90--0.70, P0.05). DTT showed that the direction and density of neural fibers were significantly asymmetrical in the natural re-covery group and the exercise training group, and more symmetrical in the exercise training group. Conclusion Early exercise can promote the neural functional recovery in rats after focal cerebral ischemia, which may associate with the improve of conduction of fibers.

Comparative Study of Focal Cerebral Ischemia Model Based on Middle Cerebral Artery Occlusion with Suture-occluded Method in Rats (review) / 中国康复理论与实践

@#There are many ways to prepare middle cerebral artery occlusion (MCAO) rat model. The focal cerebral ischemia model es-tablished by the suture-occluded method is widely accepted as an ideal focal cerebral ischemia model, which can be used in the basic and clinical study of cerebral vascular diseases. However, it still has the defects of high technical requirement, large model difference and high animal mortality. A variety of focal cerebral ischemia models were established by changing the retention time of the thread, the road the thread plugging into, the type of thread bolt and the depth of the thread plugging. This article compared different suture-occluded method, as well as the suture-occluded method to other modeling methods, different cerebral ischemia models may be different in the pathophysiology of cerebral infarction, and the effects may also be different.

Effects of Exercise Training on Learning and Memory Ability and Diffusion Tensor Imaging in Rats after Focal Cerebral Ischemia / 中国康复理论与实践

Objective To explore the effect of exercise training on learning and memory ability in rats with focal cerebral ischemia, and to analyze the changes of brain tissue structure of rats after exercise training through diffusion tensor imaging (DTI). Methods Twenty-four SPF male Sprague-Dawley rats were randomly divided into sham operation group (n=8), natural recovery group (n=8) and exercise training group (n=8). The left middle cerebral artery occlusion (MCAO) model was established. The exercise training group received running wheel training 24 hours after modeling, for 14 days. All groups were tested by the Morris water maze 15 days after modeling. The latency in the navigation experiment, as well as the first latency, boundary swimming time ratio, the boundary swimming distance ratio, the average speed and the swimming path in the space exploration experiment were recorded. Four rats with similar Longa scores in each group received rou-tine magnetic resonance imaging and DTI scanning, the fractional anisotropy (FA), axial diffusivity (λ‖), and radial diffusivity (λ⊥) of isch-emic cortex and hippocampal lesion and contralateral side were measured. Results In the navigation experiment, the latency of three groups showed a downward trend along with training days (P0.05), while it was shorter in the exercise train-ing group than in the natural recovery group in the same time (P2.627, P2.521, P0.05). The swimming paths in the exercise training group and the sham operation group were better than that of the natural recovery group. The FA and rFA in the left cortical area were higher in the sham operation group than in the exercise training group and the natural recovery group (P0.05). There was no significant difference in the FA in the right cortical area among three groups (F=0.532, P=0.607). Theλ⊥,λ‖, rλ‖and rλ⊥in the left cortical area were lower in the sham opera-tion group than in the natural recovery group (P0.05). There was no significant difference in theλ⊥andλ‖in the right cortical area among three groups (F0.05). There was no significant difference in the FA,λ⊥,λ‖and rFA, rλ⊥and rλ‖in the bilateral hippo-campal interest area among three groups (F0.05). The rFA, rλ‖, rλ⊥and leftλ⊥ were correlated with the latency in the space ex-ploration experiment in the Morris water maze test (P<0.05), in which the correlation coefficient of rλ⊥was the highest (r=0.761, P<0.01). Conclusion Proper exercise training can improve the learning and memory ability of rats with focal cerebral ischemia, and can promote the repair of nerve fiber damage and reduce the vascular edema. In addition, the rFA, rλ‖, rλ⊥andλ⊥of ischemic cortex may be predictors of cognitive function recovery in rats after focal cerebral ischemia, especially rλ⊥.

In vitro and In vivo effects of six Coptidis alkaloids on liver microsomes UGTs and UGT1A1 activities in rats and mice / 中国中药杂志

In the present study, the effects of six Coptidis alkaloids (berberine, epiberberine, coptisine, jatrorrhizine, palmatine and magnoflorine) on liver microsomes UGTs and UGT1A1 activities in rats and mice were investigated in vitro and in vivo to study the mechanism of metabolic drug-drug interactions of Coptidis Rhizoma with other drugs. In vitro rat and mice liver microsomal incubation systems combined with UDPGA were applied, as well as mice liver microsomes after administration of six Coptidis alkaloids. 4-Nitrophenol and β-estradiol were selected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. According to the in vitro rat study, berberine, epiberberine, coptisine and jatrorrhizine significantly inhibited rat liver microsome UGTs activity, particularly epiberberine showed the strongest inhibition. UGT1A1 activity was lowly inhibited by jatrorrhizine, with IC₅₀ at about 227 μmol•L⁻¹, whereas coptisine and magnoflorine significantly activated UGT1A1. According to the in vitro mice study, berberine, coptisine, jatrorrhizine and palmatine significantly inhibited mice liver microsome UGTs activity, and the six alkaloids all significantly activated UGT1A1. According to the in vivo mice study, UGTs activity was significantly activated only in berberine group, while UGT1A1 activity was significantly activated only in jatrorrhizine group. In conclusion, the effects of Coptidis alkaloids on UGT activity showed significant differences in species and between in vitro and in vivo. Meanwhile, the changes in structures of Coptidis alkaloids also have a big impact on UGT activity, which may be one of the causes for the drug-drug interactions between Coptidis Rhizoma and other drugs.

In vitro effects of Genkwa Flos chloroform extract on activity of human liver microsomes UGTs and UGT1A1 / 中国中药杂志

To predict the mechanism of liver injury induced by Genkwa Flos, we investigated the effect of chloroform extract on UGTs and UGT1A1 activities of the liver microsomes in rat and human. In the present study, 4-nitrophenol(4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC. The results showed that there were 1.00% of apigenin, 6.40% of hydroxygenkwanin and 18.38% of genkwanin in chloroform extract; and total diterpene mass fraction was 31.40%. Compared with the control group, chloroform extract could significantly inhibit the activity of UGTs in rat liver microsomes(RLM) system, while the inhibitory effect was not obvious in human liver microsomes(HLM) system. UGT1A1 activity was inhibited by chloroform extract in rat liver microsomes and human liver microsomes (based on genkwanin, IC₅₀=8.76, 10.36 μmol•L⁻¹). The inhibition types were non-competitive inhibition(RLM) and uncompetitive inhibition(HLM). In conclusion, the results indicated that chloroform extract showed different inhibitory effects on UGTs and UGT1A1 activity, which may be one of the mechanisms of liver injury induced by Genkwa Flos.

[Protective Effect of Component Compatibility Sini Decoction on Hypothyroidism Induced Renal Damage in Rats].

OBJECTIVE: To investigate the protective effect of component compatibility Sini Decoction on hypothyroidism induced renal damage in rats. METHODS: The hypothyroidism model were established by 0.1% propylthiouracil (PTU) solution 10 m/kg for consecutive 15 days. Rats were randomly divided into model group, component compatibility Sini Decoction groups[ CSD 9. 6,4. 8 and 2. 4 g/ (kg · d)] and positive control group [Euthyrox 9 µg/(kg · d)]. Radioimmunoassay was used to determine the serum T3 and T4 levels; serum BUN content was detected by UV spectrophotometer and ELISA method were used to measure the CYS-C content. The kidney was weighed, and the pathological changes of the renal were detected by HE stain. RESULTS: Compared with blank control group, kidney weight coefficient, serum T3 and T4 levels in model group were decreased, while serum BUN and CYS-C contents were increased (P < 0.05 or P < 0.01). Compared with model group, serum T3 and T4 contents were increased and serum BUN and CYS-C contents were decreased (P < 0.05) in Sini Decoction groups [CSD 9.6 and 4.8 g/(kg · d)] and positive control group. The HE stain results showed that component compatibility Sini Decoction and Euthyrox could relieve glomerular atrophy and renal tubular epithelial cell injury in rats. CONCLUSION: Component compatibility Sini Decoction has a curative effect on hypothyroidism induced renal damage in rats.

Stability study in biological samples and metabolites analysis of astragaloside IV in rat intestinal bacteria in vitro / 中国中药杂志

To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites (6-O-β-D-glucopyranosyl- cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.