RESUMO
Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments. Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue. Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis-multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2. Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.
RESUMO
BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of allograft renal function, but direct measurement of GFR remains complicated. PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE-MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT) for determination of allograft renal function. STUDY TYPE: Prospective. POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE-MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman agreement analysis. RESULTS: The reference CCr-GFR was 59.58 ± 23.72 mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 ± 34.38, 36.78 ± 14.46, 48.99 ± 23.88, and 67.32 ± 18.44 mL/min/1.73 m2 , respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals: 74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION: DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:262-269.
