ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.</p><p><b>METHODS</b>Totally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.</p><p><b>RESULTS</b>(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).</p><p><b>CONCLUSIONS</b>The ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.</p>
Subject(s)
Animals , Male , Rats , Colforsin , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Heart , Heart Failure, Diastolic , Drug Therapy , Isoproterenol , Pharmacology , Random Allocation , Rats, WistarABSTRACT
Transient receptor potential (TRP) A1, a member of TRP channel family, is activated by noxious cold. The aims of this study were to determine if TRPA1 contributed to cold-induced contractions in the isolated rat colon preparations and explore the potential mechanisms. The colon smooth muscle layers were surgically isolated from the male Wistar rats and changes in isotonic tension of longitudinal muscle under various treatments were recorded as colonic motilities. Cold stimuli were obtained by the reperfusion with Krebs-Henseleit solution at given temperature using Constant Flow Pump. The mRNA expressions of TRPA1, TRPV1 and TRPM8 in rat colon smooth muscle layer were examined by using reverse transcription-polymerase chain reaction (RT-PCR) techniques. The results showed that the contractions induced by cold stimuli (from 37 degrees C to 12 degrees C stepwise) were inversely proportional to the temperature with a maximum contraction at 17 degrees C in both proximal and distal colons (P<0.01). RT-PCR analysis revealed the expression of TRPA1, but not TRPM8 and TRPV1, in the rat proximal and distal colon smooth muscle layers. Cold-induced colonic contractions were specially inhibited by TRPA1 blocker, ruthenium red (30 μmol/L), in the proximal and distal colon (P<0.05). The cold-induced contractions of proximal (P<0.01, P<0.05) and distal colons (both P<0.001) were almost abolished or inhibited by the pretreatments of TRPA1 agonists, Allyl isothiocyanate (AITC, 300 μmol/L) and cinnamaldehyde (CA, 1 mmol/L). Extracellular calcium removal (EGTA, 1 mmol/L), PLC blocker (U73122, 10 μmol/L) and IP(3) receptor blocker (2-aminoethoxydiphenyl borate, 2-APB, 30 μmol/L) all decreased the contractions evoked by the cooling at 17 degrees C in the proximal and distal colon (P<0.001, P<0.05, P<0.001). Atropine (1 μmol/L) had no effects on these contractions. L-type Ca(2+) channels blocker nifedipine (1 μmol/L) and neurotoxin tetrodotoxin (TTX, 2 μmol/L) decreased the contractile response in the distal colon (P<0.01, P<0.05), but not in the proximal colon. In conclusion, TRPA1 contributes to cold-induced contractions of the rat colon smooth muscle, and the mechanism of TRPA1 activation involves PLC/IP(3)/Ca(2+) pathway. L-type Ca(2+) channel and neurogenic mechanism other than muscarinic receptor might be partially involved in cold-induced contraction of the distal colon, which probably resulted in higher contraction of distal colon compared with that of proximal colon.
Subject(s)
Animals , Male , Rats , Calcium Channels, L-Type , Metabolism , Cold Temperature , Colon , Metabolism , Physiology , In Vitro Techniques , Muscle Contraction , Physiology , Muscle, Smooth , Metabolism , Physiology , Physical Stimulation , RNA, Messenger , Genetics , Metabolism , Rats, Wistar , TRPA1 Cation Channel , TRPC Cation Channels , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>: To profile urinary metabolite variations from 1, 2-dimethylhydrazine (DMH)-induced precancerous colon rats, Jinfu Kang treated rats and healthy controls.</p><p><b>METHOD</b>We used ethyl chloroformate derivatization and gas chromatography-mass spectrometry (GC-MS) based metabonomic method to analyze rat urines.</p><p><b>RESULT</b>The time-dependent variations of metabolite profile showed a progressive deviation of the metabolism in the model group from the initial pattern over time and a systemic recovery of the metabolism in the treatment group, which is consistent with the histological results. The in-depth analysis indicated that the disorder of tricarboxylic acid cycle (TCA), tryptophan metabolism, polyamine metabolism and gut flora structure were associated with DMH intervention.</p><p><b>CONCLUSION</b>Metabolic study revealed that Jinfu Kang can effectively reverse metabolic departures in DMH-induced precancerous colon rat, which is consistent with pathological results.</p>
Subject(s)
Animals , Male , Rats , Colonic Neoplasms , Pathology , Colonic Polyps , Drug Therapy , Urine , Dimethylhydrazines , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Gas Chromatography-Mass Spectrometry , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of astragalus (As) on calcium accumulation and SERCA2a gene expression in left ventricular tissues in rats with pressure overload-induced cardiac hypertrophy.</p><p><b>METHOD</b>cardiac hypertrophy was induced by clipping the abdominal aorta in rats. Male SD rats were allocated to six groups: sham-operrated (Sham), aortic stenosis (Model), model +As-L (5 g x kg(-1) x d(-1)), model+As-M (10 g x kg(-1) x d(-1)), model+As-H (20 g x kg(-1) x d(-1)) and model + captopril (0.05 mg x kg(-1) x d(-1), a positive control). The drugs were administered orally from the 13 th week after surgery. Rats were examined after 12 week treatment with drugs. The cardiac hypertrophy was evaluated by left ventricular mass index (LVMI, left ventricular weight/ body weight). The calcium content in left ventricular tissue was measured by atomic absorption spectrometry. SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and protein, respectively.</p><p><b>RESULT</b>The increase of LVMI was dose-dependently lessened by As (P < 0.01, P < 0.001). The effect of As-H was similar to that of Captopril. As markedly attenuated calcium accumulation in myocardial tissure (P < 0.01). RT-PCR and Western blot results demonstrated that SERCA2a gene expressions were downregulated (P < 0.05) significantly in model group compared with sham group. As-H upregulated SERCA2a gene expressions (P < 0.05), whereas Captopril had no effect on that.</p><p><b>CONCLUSION</b>The inhibition of As on left ventricular hypertrophy induced by pressure overload in rats may partly contribute to its attenuation of calcium accumulation and up-regulation of SERCA2a gene expressions in left ventricular tissues.</p>
Subject(s)
Animals , Male , Rats , Astragalus Plant , Chemistry , Blotting, Western , Calcium , Metabolism , Drugs, Chinese Herbal , Chemistry , Pharmacology , Gene Expression Regulation , Heart , Hypertrophy, Left Ventricular , Metabolism , Myocardium , Metabolism , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of Evodia rutaecarpa water extract on ethanol-induced acute gastric lesions in rats.</p><p><b>METHOD</b>In this study, animals were intraperitoneally pretreated with vehicle (normal saline) or E. rutaecarpa at 424.8, 141.6, 47.2 mg x kg(-1). Three hours later, gastric lesions were induced by topical application of 50% ethanol for 10 min. The rat gastric transmucosal potential difference (PD) was recorded continuously by ex-vivo chamber technique. NO(x) (nitrate and nitrite) level in gastric perfusate and the length index of gastric lesions were determined in a gastric intubatton model.</p><p><b>RESULT</b>Compared with control, Evodia rutaecarpa water extract accelerated PD recovery and reduced gastric morphologic lesions in a dose-dependent manner (P < 0.05) , and also dose-dependently increased NO(x) level in gastric perfusate. Especially, at 424.8 mg x kg(-1), E. rutaecarpa promoted synthesizing of nitric oxide significantly (P < 0. 01).</p><p><b>CONCLUSION</b>E. rutaecarpa water extract showed effectively protective actions on ethanol-induced acute gastric lesions in rats, and the gastroprotective mechanisms maybe due to the strengthening action on gastric mucosal lining and the promotion of nitric oxide synthesis in local gastric mucosa.</p>
Subject(s)
Animals , Male , Rats , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Pharmacology , Ethanol , Evodia , Chemistry , Gastric Mucosa , Metabolism , Pathology , Nitric Oxide , Plants, Medicinal , Chemistry , Protective Agents , Pharmacology , Rats, Sprague-Dawley , Stomach Ulcer , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the proportion and mechanism of relieving asthma of drug partnership comprising herbal Ephedrae & Pheretima.</p><p><b>METHOD</b>To study relaxant effect on 10 micromol x L(-1) carbachol (CCh) and 10 micromol x L(-1) histamine (His) precontracted isolated tracheal rings and lowering effect on short-circuit current (Isc) increase induced by 10 micromol x L(-1) CCh with 3 proportions of 1:1, 1:3, 1:9 extract.</p><p><b>RESULT</b>1:3 proportions dose-dependently relaxed CCh-precontracted isolated tracheal rings, IC50 of 1:1, 1:3 is 7.5, 15 mg x mL(-1) respectively, 1:9 could not produce 50% inhibition effect on CCh-evoked contraction; 3 proportions also dose-dependently relaxed His-precontracted isolated tracheal rings, IC50 of 1:9, 1:3 and 1:1 is 0.19, 0.61, 1.8 mg x mL(-1) respectively. On the other hand,the orders potency of the decrease effect on CCh-evoked short circuit current increase is 1:3 > 1:1 > 1:9. The difference is not significant (P < 0.05).</p><p><b>CONCLUSION</b>Herbal Ephedrae & Pheretima had tracheal muscle relaxant and epithelium ion secretion inhibition effect, its mechanism of relieving asthma involved anti-CCh and anti-His effect 1:3 was the most appropriate dosage ratio in the anti-asthmatic drug partnership.</p>
Subject(s)
Animals , Male , Rats , Anti-Asthmatic Agents , Pharmacology , Asthma , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Pharmacology , Ephedra sinica , Chemistry , Guinea Pigs , Histamine Antagonists , Pharmacology , In Vitro Techniques , Materia Medica , Pharmacology , Muscle Relaxation , Muscle, Smooth , Oligochaeta , Chemistry , Plants, Medicinal , Chemistry , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>TO establish a RP-HPLC method for the determination of calycosin-7-O-beta-D-glucopyranoside in Radix Astragali, and to analyse the calycosin-7-O-beta-D-glucopyranoside content of ten samples of Radix Astragali, collected from different regions.</p><p><b>METHOD</b>A Polaris C18(250 mm x 4.6 mm, 5 microns) column was used and a mixture of methanol-water (30:70) was used as the mobile phase at a flow rate of 1.0 mL.min-1. The column temperature was 25 degrees C and the UV detection wavelength was 254 nm.</p><p><b>RESULT</b>The calibration curve was in good linearity over the range of 0.0106-2.12 micrograms with the regression equation Y = 3035. 97 X - 14.85(r = 0.9999). The average recovery was 95.8% (n = 5, RSD = 1.3%).</p><p><b>CONCLUSION</b>The method is simple, quick, sensitive and reproducible. In all of the samples, the calycosin-7-O-beta-D-glucopyranoside contents differ markedly.</p>