ABSTRACT
Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.
ABSTRACT
OBJECTIVE： To study the effects of Aconitum carmichaelii water extract on the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins as well as their genes in duodenum tissues of rats. METHODS： Thirty-two SD male rats were randomly divided into normal group， A. carmichaelii water extract low-dose， medium-dose and high-dose groups [0.45， 0.9， 1.8 g/（kg·d）， by crude drug]， with 8 rats in each group. They were given water and relevant liquid 0.1 mL/kg intragastrically for consecutive 7 d. After last administration， the duodenal segments of rats were collected. Western blotting assay was used to detect the expression of efflux transporters as P-glycoprotein （P-gp）， breast cancer resistance protein （Bcrp）， multidrug resistance protein 2 （Mrp2） as well as tight junction proteins as Claudin-1， Occludin and ZO-1. mRNA expression of 6 kinds of proteins relevant gene were determined by qRT-PCR respectively. RESULTS： Compared with normal group， the protein expression of P-gp， Mrp2， Bcrp， Claudin-1， Occludin and ZO-1 in duodenum of rats were increased significantly in A. carmichaelii water extract groups （P＜0.01）. mRNA expression of P-gp in A. carmichaelii water extract groups， mRNA expression of Bcrp in A. carmichaelii water extract low-dose and high-dose groups as well as mRNA expression of Claudin-1 in A. carmichaelli water extract medium-dose and high-dose groups were increased significantly， with statistical significance （P＜0.05 or P＜0.01）. There was no statistical significance in mRNA expression of other genes （P＞0.05）. CONCLUSIONS： A. carmichaelii water extract can up-regulate the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins at the level of mRNA and/or protein， thus may interact with other substrates of the aforementioned efflux transporters and drugs with cell bypass pathway as the main transport pathway. In clinical practice， adjustment of dosage may be considered in drug combination.
ABSTRACT
Objective To explore the feasibility of evaluating cardiac structure, coronary artery,pulmonary artery and cardiac function in one single scan by 320-row CT ECG-gated double phase cardiac function scan mode. MethodsForty patients underwent the 320-detector row CT double phase cardiovascular angiography. The pulmonary phase and aortic phase were reconstructed in order to evaluate the pulmonary and coronary artery. MPR reconstructions of both pulmonary and aortic phase were used to analyze the function of the two ventricles. And the results of the cardiac function were compared with those of transthoracic echocardiography. Thirty-five cases could be analyzed and diagnosed, while the other 5 cases had to be given up because of the poor imaging quality. The mean heart rate was (71.2 ± 11.2) beat per min (bpm). No arrhythmia case included. Results ( 1 ) Pulmonary embolism were diagnosed in 11 cases,coronary artery disease (CAD) were found in 5 cases, while post-stent implantation were observed in 7 cases. Six cases of congenital heart disease were diagnosed with 3 ASD and 3 primary pulmonary hypertension. Another one was diagnosed with left atrial myxoma, and 5 cases were pulmonary embolism associated with CAD. All of above cases were verified by final clinical diagnosis. (2) The heart function parameters including LVEDd , RVEDd, LVESd, RVESd and LVEF were (36.7 ±3.3), (43.3 ± 3.4) mm,(31.6±5.1), (41.3 ±5.1) mm and (47.1 ±15.1) for CT, while those were (40.3 ±3.1), (47.3 ±4.2) mm,(37.3 ±5.6), (45.3 ±3.3) mm,and (46.0 ± 14.8) for ultrasound, respectively. The CT results were correlated with the ultrasound ( n = 35, r = 0.886-0.988, P ＜ 0.01 ). (3) The average radiation exposure was ( 5.4 ± 0.5 ) mSv. Conclusions 320-row CT ECG-gated double phase cardiac function scan mode is feasible for the "one-stop-shop" examination of the cardiovascular disease. This noninvasive method is recommended for the diagnosis, differential diagnosis, treatment and prognosis of cardiovascular disease.