Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

Huoluo Yinao decoction mitigates cognitive impairments after chronic cerebral hypoperfusion in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoluo Yinao decoction (HLYND) has been used to ameliorate cognitive impairment induced by chronic cerebral hypoperfusion in clinical for years. However, the exact mechanisms remain unknown. AIM OF THE STUDY: To investigate the effects and mechanisms underlying HLYND-mediated improvement in cognitive deficits associated with chronic cerebral hypoperfusion. MATERIALS AND METHODS: Thirty-six Sprague-Dawley rats were randomly allocated to three groups: sham, model, and HLYND. Daily administration of HLYND or volume-matched vehicle by gavage was initiated 1 day after bilateral carotid artery stenosis (BCAS) and continued for 42 days. The Morris water maze (MWM) test was used to assess cognitive functions from days 36-42. Via western blot and immunofluorescent staining, restoration of neuronal plasticity and remyelination of white matter were evaluated by analyzing the expression profiles of MAP-2, synaptophysin and MBP. In addition, macrophage/microglial activation was assessed by quantifying changes in Iba1, and macrophage/microglial polarization was assessed by changes in iNOS and CD16 (M1 markers), as well as Arg1 and CD206 (M2 markers). RESULTS: In the MWM test, BCAS rats showed significantly extended escape latency and reduced platform crossing times, while those in the HLYND group had shortened escape latency and increased frequency of platform crossing. In addition, rats in the model group showed decreased levels and abnormal morphological changes of MAP-2, synaptophysin and MBP, whereas HLYND administration reversed these effects. As expected, Iba1 levels were elevated in both the model and HLYND groups but rats in the model group showed increased levels of the M1 markers, iNOS and CD16, and a correspondent decrease in the M2 marker, Arg1. In contrast, in the HLYND group, iNOS and CD16 levels were suppressed, while Arg1 levels were elevated. CONCLUSIONS: Our findings demonstrate that HLYND mitigates cognitive impairment after chronic cerebral hypoperfusion in rats through mechanisms involving increased neuronal plasticity and white matter remyelination, with a subtile modulation of macrophage/microglial polarization toward the M2 phenotype.

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients.

OBJECTIVE: To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients. METHODS: A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed. RESULTS: Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively. CONCLUSION: These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

Assessment of treatment outcomes in patients with advanced hilar cholangiocarcinoma (stages III-IV): Clinical significance of interventional therapy.

The clinical significance of palliative interventional therapy in the management of patients with advanced hilar cholangiocarcinoma (HCCA; stages III-IV) has yet to be studied. The present work was aimed to compare the clinical outcomes of the patients treated with surgery or interventional therapy.A total of 90 patients with advanced HCCA, who admitted Fuyang First People's Hospital from May 2015 to February 2016, were enrolled. Forty-five of them were assigned to the experimental group receiving biliary drainage as the interventional therapy, and the remaining 45 patients were designated as the conventional group receiving radical/palliative surgery. Before and after the treatment total bilirubin from blood was measured. The length of treatment and medical cost were also examined. All patients were followed up for at least 1 year after the treatment.For both the experimental and conventional groups, the serum bilirubin levels after treatment were significantly lower than those before treatment (P < .05); however, no significant differences between groups were seen. There were no significant differences between experimental and conventional groups in the incidence of postoperative complications and survival outcomes. Of note, the length of treatment of the experimental group was substantially shorter than that of the conventional group (P < .05). The medical expense of the experimental group was only about one-third of that of the conventional group (P < .05).Although the interventional therapy does not improve patients' survivals and reduce the incidence of complications, it significantly shortens the treatment length, reducing substantially the medical expense. This finding provides new insights into the treatment strategy for patients with advanced HCCA.

[Effect of anti-androgen and progesterone on development of regrowth antlers in 6 year old sika deer].

To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide (n=4), bicalutamide (n=4), progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed. Treatment groups were injected subcutaneously sustained-release agents of the four drugs respectively when two-branched antlers were harvested. The control group had no special treatment. In the experiment period of 60 d, blood sampleswere collected for 4 times for each deer. The concentration of testosterone in plasma was tested and analyzed to compare the changes between different groups. Development of regrowth antlers was observed. At the end of the experiment, regrowth antlers were weighted and analyzed. The resultsshowed that the weights of regrowth antlers in treatment groups were significantly greater than those from control group and the weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and 117.46% respectively in flutamide group, bicalutamide group, progesterone acetate group and melengestrol acetate group. For plasma testosterone concentration, it was not significantly different in the early stage (in the first 35 d), but at the end of the experimen, it was significantly higher than that of earlier stage (P<0.01) in various groups. Testosterone concentration of flutamide treated group was significantly lower than that of the other groups (P<0.01), while the level inbicalutamide and MGA treated groups was significantly higher than that in other groups (P<0.01). The results showed that both anti-androgen drugs and MGA treatment promoted the development of regrowth antlers and increased the weight of regrowth antlers, where the effect was most significant by MGA treatment. From the morphological observation of the antlers, it was found that anti-androgen and MGA treatments prolonged the growth period of regrowth antlers through delaying the ossification of antlers. However, plasma testosterone concentration was not affected by the treatments.

RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Ribosome biogenesis regulatory protein homolog (RRS1) is an essential factor involved in ribosome biogenesis, while its role in CRC remains largely unclear. Here, we found that RRS1 expression was significantly higher in CRC tissues compared with adjacent normal tissues. RRS1 High expression also predicted poor overall survival of CRC patients. Knockdown of RRS1 induced the G2/M cell cycle arrest, apoptosis and suppressed the proliferation of RKO and HCT-116 CRC cells. Furthermore, angiogenesis was also reduced in CRC cells after RRS1 knockdown. In addition, suppression of RRS1 blunted the tumor formation of CRC cells in nude mice. At the molecular level, silencing of RRS1 decreased the expression of M-phase inducer phosphatase 3 (CDC25C), Cyclin-dependent kinase 1 (CDK1), antigen KI-67 (KI67) and increased the protein level of cyclin-dependent kinase inhibitor 1 (CDKN1A) and tumor suppressor p53 (p53). Taken together, our findings provide evidence that RRS1 may promote the development of colon cancer. Therefore, targeting RRS1 may be a promising therapeutic strategy for CRC patients.

Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by miR-203 in hepatocellular carcinoma.

RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in various types of cancer. It has previously been demonstrated that RASAL2 is hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern of RASAL2 and its potential role in HCC remain to be elucidated. The present study demonstrated that the expression of RASAL2 was upregulated in HCC tissues, compared with in normal liver tissues, by using immunohistochemistry. In addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of RASAL2 inhibited the growth and invasion of HCC cells. Western blotting results indicated that the inhibition of RASAL2 reduced the levels of phosphorylated-AKT. Notably, RASAL2 was observed to be a direct target of miR-203 in HCC in luciferase activity assays. Furthermore, overexpression of miR-203 exhibited a similar effect to RASAL2 knockdown in HCC cells. These results indicated that RASAL2 serves a tumor oncogenic role in HCC and may be considered a potential target in HCC.

[Therapeutic efficiency of transsubperiosteal approach for excision of orbital cavernous hemangiomas].

OBJECTIVE: To evaluate the indications, operative skills and effects of transsubperiosteal approach for excision of orbital cavernous hemangiomas (OCH). METHODS: In a retrospective study, the records of 42 cases with OCH confirmed by pathologic examination between June 2004 and June 2010 were analyzed. Preoperative diagnoses were based on clinical signs, CT and MRI examinations. According to the locations of the tumor, patients were assigned to 4 groups: group I: tumors located in the superotemporal quadrant in 18 cases; group II: tumors located in or near the superior orbital fissure in 15 cases; group III: tumors in the inferior peripheral space extending to the orbital apex in 4 cases; group IV: tumors in the inferonasal quadrant in 5 cases. In all 4 groups the periorbital skin was incised and then the periosteum of orbital rim was exposed. Tumors were removed from subperiosteal space. The complications and follow-up results were recorded. RESULTS: The rate of preoperative correct diagnosis was 100%. All cases were cured by once surgical procedures for average 20-30 min. Thirty-eight (90.5%) tumors were removed intact. The deblocking removal was recorded in 4 (9.5%) cases. In order to improve the surgical exposure of orbital apex in group II, superolateral orbital rim was removed in 6 (14.3%) cases and the walls were drilled in 3 (7.1%) cases. Follow-up periods ranged 1 to 7 years. No recurrent or remnant was recorded on imaging reviews. The visual acuity was improved in 6 (14.3%) cases. The temporary complications included chemosis in 9 (21.4%) cases, limited ocular movement in 4 (9.5%) cases and ptosis in 3 (7.1%) cases. The permanent complications included limited ocular extreme movement and dilated pupil, both in 2 cases (4.7%). CONCLUSIONS: Transsubperiosteal approach is eligible for the removal of OCH in the superotemporal, inferonasal quadrant and the floor of the orbit and is recommended for the tumors near the superior orbital fissure. This approach is safe and effective for removal of OCH with less surgical complication.

Activity limitation and participation restrictions of breast cancer patients receiving chemotherapy: psychometric properties and validation of the Chinese version of the WHODAS 2.0.

PURPOSE: This study sought to determine the psychometric properties of the Chinese version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in a sample of 402 primary breast cancer patients receiving chemotherapy after surgery. METHODS: Four-hundred and two subjects were interviewed with the Chinese version of the WHODAS 2.0. Patients also completed the Functional Assessment of Cancer Therapy-Breast (FACT-B). Internal consistency reliability was measured by Cronbach's α. Spearman correlation coefficients between total scores and subscales of FACT-B and WHODAS 2.0 were examined to get the convergent validity. Independent sample t test was applied to test discriminant validity by comparing the difference of disability scores for different degree of relevant symptoms. The factor structure of the WHODAS 2.0 was examined by exploratory factor analysis (EFA) and confirmatory factor analysis. RESULTS: The Chinese version of the WHODAS 2.0 showed satisfactory internal consistency (r, 0.72-0.92), convergent validity and discriminant validity. After 4 items(item D2.2: standing up; D3.3: eating; D4.5: sexual activities; and D6.3: living with dignity) were excluded, EFA identified seven separate factors for 'Self-care and Household activities,' 'Getting along with people,' 'Getting around,' 'Understanding,' 'Communicating,' 'Participation in society' and 'Family burden'(explained variance 72.13 %). The reduced model also presented the best fit [confirmatory fit index = 0.914, Tucker-Lewis index = 0.900, root mean square error of approximation = 0.069] compared with the model suggested by EFA and hypothesized a prior. CONCLUSIONS: Overall, the Chinese version of the WHODAS 2.0 is a reliable and valid instrument for measuring activity limitation and participation restrictions in Chinese breast cancer patients receiving chemotherapy.

AKT/GSK3ß-dependent autophagy contributes to the neuroprotection of limb remote ischemic postconditioning in the transient cerebral ischemic rat model.

BACKGROUND: Limb remote ischemic postconditioning (RIPostC) has been recognized as an applicable strategy in protecting against cerebral ischemic injury. However, the time window for application of limb RIPostC and the mechanisms behind RIPostC are still unclear. AIMS: In this study, we investigated the protective efficacy and the role of autophagy in limb RIPostC using a transient middle cerebral artery occlusion rat model. RESULTS: Limb RIPostC applied in the early phase of reperfusion reduced infarct size and improved neurological function. Autophagy levels in penumbral tissues were elevated in neurons of limb RIPostC rats, with an increase in the phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß). Blocking the AKT/GSK3ß pathway via the AKT inhibitor LY294002 prior to limb RIPostC suppressed the RIPostC-induced autophagy and resulted in the activation of caspase-3 in RIPostC rats, suggesting a critical role for AKT/GSK3ß-dependent autophagy in reducing cell death after cerebral ischemia. CONCLUSIONS: These results aid optimization of the time window for RIPostC use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIPostC.

[Clinical analysis of 25 cases of intraorbital nonmetallic foreign bodies].

OBJECTIVE: To evaluate the clinical features, diagnostic methods and treatment of intraorbital nonmetallic foreign body injuries. METHODS: In a retrospective study, the records of 25 consecutive cases with nonmetallic foreign bodies in the orbit confirmed by surgery were analyzed with special attention to the types of injury, history, clinical manifestations, imaging findings, treatment and follow-up results. RESULTS: Among 25 cases with nonmetallic foreign bodies, 23 cases were caused by trauma, including 11 cases with wooden bodies, 3 cases with glass, grease, or stone, 2 cases with plastic pen point, and one case with fire crackers. The remaining two cases had iatrogenic foreign bodies. The distinctive clinical manifestation was the periorbital fistula recorded in 11 (44%) cases, mostly in patients with wooden foreign bodies. The CT findings were different in various foreign bodies. The wooden foreign bodies showed low density in the acute stage and the density increased gradually from the acute to the chronic stage. CT images with lower windows could distinguish a wooden foreign body better. The grease was seen as low density mimicking orbital fat on CT. The stone or glass showed as masses with high density. Wooden foreign bodies displayed low signals on both MRI T1- and T2-weighted images. The surrounding pus was seen as a ring with high signal on T2-weighted images. The inflammatory infiltration showed marked enhancement. The grease displayed high signal on both T1- and T2-weighted images and showed lower signal than that of the fat. All patients underwent surgical removal of retained foreign bodies and the surrounding decomposed tissues. The infected wounds were not sutured at one stage operation. After follow-up for 6 months, all wounds healed normally and all patients recovered well. No complications were encountered. CONCLUSIONS: There are various types of intraorbital nonmetallic foreign bodies. The clinical manifestations of these different foreign bodies are complex. CT is the preferred examination for this condition. With the combination of correct diagnosis, proper surgical skills, and complete removal of foreign bodies and surrounding decomposed tissues, nonmetallic foreign bodies can be treated efficiently.

Toxic effects caused by rhubarb (Rheum palmatum L.) are reversed on immature and aged rats.

AIM OF THE STUDY: Rhubarb is generally used to people of broad age, but diverse responses of people at different age to rhubarb have been little clarified. In this study, an attempt was made to access the safety of rhubarb to both immature and aged rats to provide some references for its clinical usage. MATERIALS AND METHODS: The total extract of rhubarb was administered intragastricly to both immature and aged rats once a day and lasted for 5 weeks. Then histopathologic and biochemical examinations were performed. RESULTS: No death was observed in immature rat groups, while 23.3% (21/90) subjects in aged rat groups died and most of the death cases were observed in the high-dosage (40 gkg(-1) of body weight per day od, counted on the quantity of crude material) group. The death rate between aged and immature rats was found of significantly statistical difference. Dosage-dependent histopathologic changes in kidney were observed in all the rhubarb-treated rats, principally involving the proximal tubules. Kidney changes in aged rats were severer than those observed in immature ones. Hepatic cells necrosis was occasionally observed in the middle- and high-dosage aged rat groups and minimal biliary hyperplasia was found in all the rhubarb-treated aged rats. Increased incidences of activated Kupffer cells and lymphocytic infiltration were found in all the rhubarb-treated rats. And dosage-dependent increase of interleukin 6 (IL-6) and notable increase of IL-8 was found in aged rat groups. CONCLUSIONS: The immature and aged rats showed reversed responses to the toxic potential of rhubarb extract. Elderly subjects were susceptible to the toxicity of high-dosage rhubarb, which drove rigorous consideration on rational use of rhubarb to aged people.

[Cloning and expression of novel swine gene BCL-G(L) in E.coli and preparation of its polyclonal antibody in guinea pigs].

AIM: In order to express a novel gene named as BCL-G(L); of swine in E.coli and prepare its polyclonal antibody. METHODS: The contig sequence of the gene was predicted and in silicon cloned by blasting the human BCL-G(L); in swine ESTs database in NCBI. The cloning sequence was obtained by RT-PCR from swine spleen. The cloning sequence was identified by sequencing and compared with the contig sequence. Then the gene was cloned into a prokaryotic expression vector pET-32a to construct a recombinant plasmid named as pET32a-BCL-G(L);. The fusion protein pET32a-BCL-G(L); was expressed in E.coli BL21 and purified using a His-tag fusion protein purification kit. Then guinea pigs were immunized with the purified protein to get the specific polyclonal antibody. RESULTS: The titer of the antibody was 1:800 detected by ELISA. The protein BCL-G(L); can be specifically detected by western blot assay using the polyclonal antibody. CONCLUSION: The novel swine gene BCL-G(L); was cloned and expressed in E.coli and its polyclonal antibody was prepared successfully.

[Clinical manifestations, diagnosis and management of recurrent orbital dermoid cysts].

OBJECTIVE: To evaluate the clinical features, diagnostic methods and treatment of recurrent orbital dermoid cysts. METHODS: In a retrospective study, the records of 30 consecutive cases with recurrent orbital dermoid cyst confirmed by pathologic examination were analyzed with special attention to the case histories, recurrent factors, clinical manifestations, imaging findings, treatment and prognosis. RESULTS: In the present series, the interval from first appearance in our institute to the operation ranged from 1 month to 36 years, with a median of 2.5 years. Once, twice and three times of operation history were noted in 20 cases, 9 cases and 1 case, respectively. The clinical characteristics included: periorbital masses with red swelling and tenderness in 16 cases, cutaneous fistulas in 4 cases, ectropion and adherence of upper lid in 4 cases. The risk factors for the recurrence included the incomplete excision the cyst or residual of the cyst wall in the bone sutures in 16 cases, misdiagnosis as subcutaneous mass leading to inappropriate operations in 11 cases, operation without imaging examinations in 8 cases, etc. CT scan was performed in all cases, which showed dermoid cysts with hypodensity or isodensity. The common imaging signs included dumbbell dermoid cysts located near the zygomaticofrontal suture in 8 cases, slender and circuitous tunnel within the orbital wall in 6 cases, and extensive and wavy impression of the bony walls in 6 cases. Surgical excision was performed in 28 cases and conservation therapy was used in 2 cases. Cystic content and wall were removed thoroughly during the operation. Follow-up ranged from 1 to 9 years and no recurrence or serious complications were noted. CONCLUSIONS: The recurrence of orbital dermoid cysts is correlated with various factors. The importance of recognition of clinical features and imaging findings of this tumor should be emphasized. With the guide of imaging examinations and the combination of various surgical skills, the recurrence of dermoid cysts could be prevented efficiently.

[Diagnosis and management of the tumors of extraocular muscles].

OBJECTIVE: To evaluate the spectrum, clinical features, diagnostic methods and treatment of the tumors of extraocular muscles. METHODS: In a retrospective case series study,the records of 11 consecutive cases with tumors of the extraocular muscles confirmed by pathologic examination were analyzed with special attention to the clinical manifestations, imaging findings, treatment and prognosis. RESULTS: There were fibromatosis in 3 cases, intermuscular hemangioma and granular cell tumor both in 2 cases, inflammatory myofibroblastic tumor, rhabdomyosarcoma, T cell lymphoma and metastatic adenocarcinoma all in 1 case. The most frequent symptoms were limited ocular movement, exophthalmos and ocular displacement. In respect to images of computed tomography or magnetic resonance imaging, the configuration of the extraocular muscles with tumors demonstrated 3 patterns, fusiform, globular and irregular. The tumors that involved inferior, medial and lateral rectus muscles, and inferior oblique muscle, their maximal diameters all exceeded 1 cm. Depending on the involved muscles, different operative approaches were applied. The choice of treatments was determined by the pathology of the tumors. CONCLUSIONS: The spectrum, clinical features and imaging findings of the tumors of extraocular muscles are unique. Earlier biopsy is important. The prognosis is correlated with treatments and the characteristic of tumors.

[COLD and HOT nature of Coptis & Evodia and their prescriptions investigated with diet restriction/cold-water swimming mice models].

To establish a new method to evaluate the COLD and HOT nature of Coptis & Evodia and their prescriptions Zuojinwan and Fanzuojinwan. Physical models of mice were established by diet restriction with cold-water swimming (weak model, WM) and fed with high protein animal feeds (strong model, SM). An instrument with cold and hot pads was used to investigate the variation of temperature tropism among SM and WM groups of mice affected by drugs. Meanwhile, the oxygen consumption and activity of adenosine triphosphatase (ATPase) were detected, in order to investigate the mechanism of energy metabolism which might be affected by these drugs. The results showed that the drug effects gradually changed in an order of "Coptis-->Zuojinwan--> Fanzuojinwan-->Evodia". In detail, Coptis increased the remaining rate (RR) of mice on hot pad, decreased oxygen consumption and ATPase activity (n=6, P < 0.01 or P < 0.05), while Evodia performed inversely; which indicated the COLD nature of Coptis and HOT nature of Evodia, and confirmed with their traditional definition in medicinal works. In conclusion, the methods applied in this work, can objectively and directly express the nature disparity between the two herbs and predict the tendency of changes of the nature of their combination, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.

[Effect of berberine on left ventricular remodeling in renovascular hypertensive rats].

The purpose of this study is to evaluate the effects and the underline mechanisms of berberine on the cardiac function and left ventricular remodeling in rats with renovascular hypertension. The renovascular hypertensive model was established by the two-kidney, two-clip (2K2C) method in Sprague-Dawley (SD) rats. Two weeks after surgery, all the operated SD rats were randomly assigned into four groups: (1) renovascular hypertensive model group; (2) berberine 5 mg x kg(-1) group; (3) berberine 10 mg x kg(-1) group; (4) captopril 45 mg x kg(-1) group; and the sham operated rats were used as control. Four weeks after the drugs were administered, the cardiac function was assessed. The ratios of heart weight to body weight (HW/BW), left ventricular weight to body weight (LVW/BW) and right ventricular weight to body weight (RVW/BW) were compared between groups. Coronal sections of the left ventricular tissue (LV) were prepared for paraffin sections, picrosirius red and HE staining was performed. The left ventricular wall thickness (LVWT), interventricular septal thickness (IVST), the parameters of myocardial fibrosis indicated by interstitial collagen volume fraction (ICVF) and perivascular collagen area (PVCA) were assessed. Nitric oxide (NO), adenosine cyclophosphate (cAMP) and guanosine cyclophosphate (cGMP) concentrations of left ventricular tissue were measured. Berberine 5 mg x kg(-1) and 10 mg x kg(-1) increased the left ventricular +/- dp/dt(max) and HR. Berberine 10 mg x kg(-1) decreased HW/BW and LVW/BW. The image analysis showed that both 5 and 10 mg x kg(-1) of berberine decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left ventricular tissue. Berberine could improve cardiac contractility of 2K2C model rats, and inhibit left ventricular remodeling especially myocardial fibrosis in renovascular hypertension rats. And such effects may partially associate with the increased NO and cAMP content in left ventricular tissue.