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Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.
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Objective To establish an HPLC method for the simultaneous determination of 10 components in the active parts of Uygur medicine Dracocephalum Moldavica L.Methods The determination was performed on a Shim-pack ODS(4.6 mm×250 mm,5 um)column with the mobile phase consisting of acetonitrile(A)-0.5%formic acid(B)in aqueous solution in a gradient elution mode(0-30 min,17%A;30-60 min,17%→ 28%A;60-78 min,28%A)at a flow rate of 1.0 mL·min-1.The temperature of the chromatographic column was 35℃and the detection was monitored by a UV detector at 330 nm.Results Cof-feic acid,p-coumalic acid,cynaroside,luteolin-7-O-β-D-glucuronide,apigenin 7-O-glucuronide,rosmarinic acid,diosmetin7-O-β-D-glucuronide,salvianolic acid A,tilianin,apigenin were well separated under this chromatographic condition,and the linear relation-ship were good in the concentration range examined(r>0.999 2).The overall recoveries ranged from 91.83%to 106.43%with the RSD ranging from 0.38%to 2.22%.Conclusion The established content determination method is highly accurate and reproduci-ble,and suitable for the analysis and quality control of the active parts of Dracocephalum Moldavica L.
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Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.
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OBJECTIVE:To study the effects of tilianin(TIL)on brain tissue in rats with cerebral ischemia-reperfusion injury. METHODS:Totally 120 male SD rats were randomly divided into sham operation group(0.9% sodium chloride solution),model group(0.9% sodium chloride solution),nimodipine group(32 mg/kg)and TIL low-dose and medium-dose,high-dose groups(4, 8,16 mg/kg),with 20 rats in each group. The rats were given relevant medicine intragastrically,once a day,for consecutive 7 d. 15 min after last medication,cerebral ischemia-reperfusion injury model was established by reforming suture-occluded method. The neurological deficit score in rats were evaluated, and percentage of cerebral infarction volume of rats was determined. Histopathological changes of brain tissue were observed by HE staining. The activities of SOD,CAT and LDH,MDA content in cerebral tissue of rats were determined. The expression of calcitonin gene-related peptide(CGRP)and peripheral vascular endothelial growth factor receptor 2 (VEGFR2) protein were determined by Western blot assay. RESULTS:Compared with sham operation group,neurological deficit score and percentage of cerebral infarction volume of model group were increased significantly(P<0.01);the nerve cells in brain tissue were significantly reduced and the interstitial edema was obvious. SOD and CAT activities were decreased significantly,LDH activity was increased significantly,MDA content was decreased significantly,protein expression of CGRP and VEGFR2were increased significantly(P<0.05 or P<0.01). Compared with model group,neurological deficit score of nimodipine group,TIL medium-dose and high-dose groups were decreased significantly;percentage of cerebral infarction volume was decreased significantly (P<0.05 or P<0.01);above pathological conditions of cerebral tissue in rats were relieved significantly;SOD and CAT activities were strengthened significantly,MDA content and LDH activities were decreased significantly,protein expression of CGRP and VEGFR2were increased significantly (P<0.05 or P<0.01). CONCLUSIONS: TIL has certain protective effects on cerebral ischemia-reperfusion injury model rats,and its mechanism may be related to the up-regulation of CGRP and VEGFR2expression.