Objective:To investigate the role of melatonin in calcium overload-induced heart injury.Methods:Thirty-two rats were divided into 4 groups:a control group (Control),a melatonin control group (Mel),a calcium overload group (CaP),and a calcium overload plus melatonin group (Mel+CaP).Isolated Sprague Dawley male rat hearts underwent Langendorffperfusion.Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance.Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium.Lactate dehydrogenase (LDH) activity in the coronary flow was determined.The expressions of caspase-3 and cytochrome c were determined by Western blot.The pathological morphological changes in myocardial fiber were analyzed by HE staining.Results:Compared with the control group,calcium overload significantly induced an enlarged infarct size (P＜0.01),accompanied by the disordered arrangement of myocardial fiber,up-regulation of cytochrome c and caspase-3 (P＜0.01),and the increased activity of LDH (P＜0.01).T hese effects were significantly attenuated by 10 μmol/L melatonin (P＜0.01).Conclusion:Melatonin can alleviate calcium overload-induced heart injury.

Objective To observe the cardiosomatic motor reflex (CMR)of rats, and to clarify the descending modulation of nucleus raphes magnus (NRM)in cardiac nociception and its pathway.Methods 34 male healthy SD rats were randomly divided into NRM electrical stimulation group (n=8 ), NRM stimulation combined with dorsolateral funiculus (DLF ) transection group (n= 8 ), NRM stimulation combined with antagonist of 5-hydroxytryptamine (5-HT)methysergide intrathecal administration group (n=18).The rat model of CMR was established through inj ecting capsaicin into the pericardial sac of the rats in various groups. The electromyogram (EMG) response of dorsal spinotrapezius muscle was used as detection index, and by placing the stimulation electrode in NRM and (or)intrathecal catheterization, the descending inhibitory modulation of NRM in CMR and the influence of DLF tansection or methysergide intrathecal administration in descending inhibitory modulation of NRM were observed.Results Compared with before stimulation,the EMG response was decreased after NRM electrical stimulation (75 μA) (P<0.05 );after bilateral DLF transection, the EMG response after NRM stimulation was significantly increased compared with before DLF transection (P<0.05 ), and there was no significant difference compared with its control (P> 0.05 ). In addition, after intrathecal administration of methysergide,the EMG response after NRM stimulation was significantly increased compared with before intrathecal treatment of methysergide (P<0.05),but it was still significantly smaller than that of its control (P<0.05). Conclusion Cardiac nociception evoked by capsaicin stimulation is subject to descending inhibitory modulation from NRM,and the descending inhibition from NRM is conveyed via the DLF and partially mediated by endogenous 5-HT system.

Objective To observe whether or not long-term inhalation of nitrous oxide can affect the cardiac function in rats. Methods Sprague-Dawley rats of either sex were randomly divided into four groups. Group A: inhaled common air for 50 days as control; Group B: inhaled 500mL/L N_2O for 15 days, two hours every day; Group C: inhaled 500mL/L N_2O for 30 days, two hours every day; Group D: inhaled 500mL/L N_2O for 50 days, two hours every day. Float glass intracellular microelectrode recording technique was used for observation of the duration (MAPD_(90), MAPD_(50) and MAPD_(20)) and amplitude of action potentials (APs) of left ventricular muscle cells in vitro. Angiotensin-2 (Ang-2) and eNOS were detected by immunohistochemical technique. Results ① Compared with that in Group A, the Aps duration of left ventricular muscle cells (MAPD) in Group B had no significant change while the MAPDs in Group C and Group D were extended significantly. There were no significant differences among the four groups in Aps amplitude. ② The expression of Ang-2 did not differ significantly between Group B and Group A. The expression level was higher in Group C and D than in Group A. ③ The expression level of eNOS was significantly lower in Group C and D than in Group A (P<0.05). Conclusion Long-term inhalation of N2O can significantly affect the cardiac function in rats, which may be related to higher expression of AngⅡin the heart induced by the long-time excitation of sympathetic nerves.

Aim ToinvestigatetheeffectsofCa2+/calmodulin-dependent protein kinase Ⅱ inhibitor KN-93 on calcium overload-induced heart injury.Methods Thirty-twoisolatedratheartswererandomlydivided into the control group,KN-93 control group,calcium paradox group,and calcium paradox with KN-93 treat-ment group.Left ventricular pressure were recorded, and the heart function was evaluated by the left ventric-ular end-diastolic pressure (LVEDP ) and developed pressure (LVDP).Coronary flow (CF)were collect-ed,and lactate dehydrogenase (LDH)content was de-termined.Triphenyltetrazolium chloride staining was usedtomeasuretheinfarctsize.Results Compared with the control group,KN-93 at 2. 5 μmol·L-1 had no effects on coronary flow,cardiac performance and cell death at the end of perfusion in normal rats (P>0. 05 );The hearts of calcium paradox exhibited a de-crease in LVDP and CF,meanwhile an increase in LV-EDP,LDH,and infarct size of 18 ±7. 2% (P <0. 01).2. 5 μmol·L-1 KN-93 further increased the levels of LVEDP,LDH and infarct size (P<0. 01)in Ca2+paradoxical hearts,while it provoked the decline intheCFandLVDP(P<0.01).Conclusion The data demonstrates that KN-93 aggravates heart injury in calcium paradox,it also suggests that CaMKⅡ is in-volved in the Ca2+overload-induced heart injury.

OBJECTIVETo investigate the role of ventrolateral periaqueductal gray (VL-PAG) metabotropic glutamate receptors subtype 7 and 8 (mGluR 7/8) in descending modulation of cardiosomatic motor reflex (CMR) in rats.

METHODSAMN082 (agonist of mGluR 7) and DCPG (agonist of mGluR 8) were injected into the VL-PAG of a rat model of CMR to observe their effects in modulating CMR. The raphe magnus nucleus (NRM) or the gigantocellular reticular nucleus (Gi) was then damaged, and the changes in VL-PAG descending modulation were observed.

RESULTSSelective activation of mGluR 7 of the VL-PAG by AMN082 obviously facilitated capsaicin (CAP)-induced CMR (P<0.05), which was suppressed by DCPG-induced mGluR 8 activation (P<0.05). These facilitatory or inhibitory effects were completely reversed by group III mGluR antagonist MSOP. Damaging the NRM of VL-PAG main relay nucleus did not significantly affect the facilitatory effect produced by AMN082 microinjection (P>0.05), but partially attenuated the inhibitory effect of DCPG microinjection (P<0.05). Both the facilitatory effect of AMN082 and the inhibitory effect of DCPG were reduced obviously after bilateral Gi damage (P<0.05).

CONCLUSIONVL-PAG mGluR 7 and mGluR 8 mediate biphasic regulation of CMR in rats probably through activation of different sub-nuclei and different neurons in the rostroventral medulla.

Animals ; Benzhydryl Compounds ; pharmacology ; Benzoates ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Male ; Medulla Oblongata ; metabolism ; Periaqueductal Gray ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate ; agonists ; metabolism ; Reflex ; physiology

OBJECTIVETo observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats.

METHODSA rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electrically stimulated (25, 75 and 100 µA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception.

RESULTSElectrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 µA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 µA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group.

CONCLUSIONCardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.

Animals ; Capsaicin ; pharmacology ; Electric Stimulation ; Electromyography ; drug effects ; Male ; Medulla Oblongata ; physiology ; Nociception ; Nociceptors ; drug effects ; physiology ; Pain ; physiopathology ; Pericardium ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Sensory System Agents ; pharmacology

Objective:To investigate the role of Na+/Ca2+ exchanger (NCX) in myocardial ischemiareperfusion injury and the underlying mechanisms.Methods:Forty Sprague-Dawley rats were divided into 4 groups randomly:a control group,a KBR7943 group,an ischemia-reperfusion group (IR group),and an IR plus KB-R7943 group (KB-R7943+IR group).Isolated Sprague Dawley male rat hearts underwent Langendorffperfusion.The ratio of left ventricular developed pressure (LVDP),left ventricular end-diastolic pressure (LVEDP),the infarct size of myocardium,and the lactate dehydrogenase (LDH) activity in the coronary flow was determined.HE staining was used to assess the change of myocardial morphology.Western blot was used to determine the levels of cleaved caspase-3,cytochrome c and the phosphorylation of Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and the Thr17 site ofphospholamban.Results:Compared with the control group,IR group significantly induced an enlarged infarct size,reduction of the ratio of LVDP,up-regulation of cytochrome c,cleaved caspase-3,p-CaMKⅡ and p-phospholamban,and increased in the activity of LDH,the level of LVEDP (P＜0.01) and the disordered myocardial morphology.These effects were significantly attenuated in the presence of KB-R7943 treatment (10 μmol/L).Conclusion:NCX mediates myocardial ischemia-reperfusion-induced cell apoptosis and necrosis through activation of CaMKⅡ.

Objective To investigate the relationship between serum indexes and the degree of liver fibrosis in chronic hepatitis B(CHB)patients with HBeAg-negative and normal ALT,and to establish a new non-invasive model for predicting liver fibrosis in CHB patients.Methods The clinical data of 679 HBeAg-negative chronic HBV infected patients with normal ALT who underwent liver biopsy from October 2012 to December 2021 were retrospectively analyzed.Among these patients,they were categorized into the control group(S1,observation group)the and significant fibrosis group(S2/S3/S4,control group)based on liver biopsy results.The LASSO regression model was used for covariates selection and the restricted cubic splines model was used to examine nonlinear associations between covariates and outcomes.We used Logistic regression models to establish predictive models.Results Liver biopsy showed that 48.7%of the patients had obvious fibrosis(S≥2).GGT shows a nonlinear relationship with the degree of liver fibrosis.AST and PT show a positive relationship with the liver fibrosis degree,respectively.The area under the ROC curve(AUC)of GGT + PT + AST is 0.68(95%CI:0.64～0.72),and this model performed better than models established using GPR,APRI,and FIB-4.Conclusion The prediction model of GGT + PT+AST has high predictive value on the severity of liver fibrosis among CHB patients whose HBeAg is negative.

Xihuang pills are a classic Chinese patent medicine following the theoretical principle of combining eliminating pathogen with reinforcing healthy qi in both local areas and the whole body， with the effects of clearing heat， detoxifying， alleviating edema， and dissipating mass. This medicine is traditionally used for treating carbuncle， furuncle， multiple abscess， carcinoma of breast， phlegm nodule， scrofula， lung abscess， and intestine abscess caused by fire depression， phlegm stasis， and heat toxin stagnation. It is used for treating malignant tumors， breast hyperplasia， herpes zoster， lymphadenitis， pelvic inflammatory disease， mastitis， vocal cord leukoplakia， and acne in modern medicine. Xihuang pills are now included in the 2020 edition of the Chinese Pharmacopoeia. The use of high-quality medicinal materials and modern technology enables full retaining of the active components in the medicinal materials. The chemical components in this medicine mainly include amino acids， terpenoids， fatty acids， fatty acid esters， phenols， bile acids， bile pigments， and volatile oils. Modern pharmacological studies have shown that a variety of active components such as bilirubin， bile acid， boswellic acid， and volatile oil in Xihuang pills interact with each other to exert anti-tumor， anti-breast hyperplasia， immunomodulatory， anti-inflammatory， and neuroendocrine-regulating effect. This paper reviews the research progress in the active components and pharmacological effects of Xihuang pills and predicts the quality markers （Q-markers） of this medicine according to the transmission， traceability， specificity， efficacy， measurability， and compound compatibility in the concept of Q-marker. It is suggested that bilirubin， bile acid， taurine， muskone， 11-carbonyl-β-boswellic acid， β-boswellic acid， 3-acetyl-11-keto-β-boswellic acid， octyl acetate， β-elemene， and myrrhone can be used as Q-markers of Xihuang pills， which can provide a basis for research on the material basis and the quality control of Xihuang pills.