RESUMO
OBJECTIVE：To study the effects of couplet medicine of Rheum p almatum-Salvia miltiorrhiza on the contents of enterogenous urotoxin and intestinal barrier function in chronic renal failure （CRF）model rats. METHODS ：Totally 55 male Wistar rats were randomly divided into sham operation group （10 rats）and modeling group （45 rats）. In sham operation group ，the kidneys were isolated but not removed ；CRF model was reproduced by 5/6 nephrectomy in modeling group. After modeling （excluding 5 dead and non-modeling rats ），modeling rats were divided into model group （water），Niaoduqing granules group （2.5 g/kg），couplet medicine of R. palmatum -S. miltiorrhiza groups（6，3 g/kg，by crude drug ），with 10 rats in each group. Sham operation group and model group were given constant volume of water intragastrically. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 12 weeks. After last administration ，the contents of creatinine （Scr）and urea nitrogen（BUN）in serum ，the content of urinary creatinine （Ucr） in urine were determined by automatic biochemical analyzer；creatinine clearance rate （Ccr）was calculated. The contents of enterogenous urotoxin [trimethylamine-N-oxide （TMAO），indoxyl sulfate （IS）and p-cresyl sulphate （PCS）] were determined by UPLC-ESI-MS/MS. Real-time RT-PCR and immunofluorescence assay were used to detect the mRNA and protein expression of Occludin and ZO-1 in the ileum tissue. HE staining and Masson staining were used to observe the pathologi cal changes of renal tissue. The ultrastructural changes of rat colon were observed by transmission electron microscope. RESULTS ：Compared with sham operation group ，serum contents of Scr，BUN，TMAO，PCS and IS were increased significantly in model group （P＜0.01），while urine content of Ucr ，Ccr，mRNA and protein expression of Occludin and ZO- 1 in ileum tissue were decreased significantly （P＜0.01）；renal glomerulosclerosis ， renal tubules dilation and inflammatory invasion and fibrosisin the interstitium were all found ；the intestinal epithelial barrier structure of colon tissue was severely damaged. Compared with model group ，serum contents of Scr ，BUN，TMAO，PCS and IS were decreased significantly in administration groups （P＜0.05 or P＜0.01）；the mRNA and protein expression of Occludin and ZO-1 in the ileum tissue were increased significantly （except for mRNA expression of ZO- 1 in R. palmatum -S. miltiorrhiza low-dose group （P＜0.05 or P＜0.01）；the infiltration of inflammatory cells in renal interstitium ，the degree of fibrosis and the damage of intestinal epithelial barrier structure in colon tissue were reduced. CONCLUSIONS ：Couplet medicine of R. palmatum -S. miltiorrhiza can effectively protect the residual renal function of CRF model rats ，the mechanism of which may be associated with reducing the serum contents of enterogenous urotoxin ，up-regulating mRNA and protein expresssion of Occludin and ZO- 1 in the ileum tissue so as to improve intestinal barrier function.
RESUMO
OBJECTIVE：To preparea novel Curcumin （Cur）dry powder inhalation （DPI）loaded by nanoporous flower-shaped lactose（FL），and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs. METHODS ：FL-loaded Cur （Cur-FL） compound powder was prepared by solution adsorption method. Using drug-loading amount and adsorption rate as indicators ，single-factor experiment was used to optimize Cur concentration，Cur-FL ratio （m/m）and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder. Fourier transform infrared spectroscopy ，scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology. The water content and aerodynamic properties were determined ；in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid. RESULTS ：The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL，Cur-FL ratio of 1 ∶ 4，adsorption time of 1 h. The drug-loading amount of compound powder was （23.37±0.43）％，the encapsulation rate was （91.64±0.44）％，and the adsorption rate was （30.50±0.72）％. Cur-FL particles were flower shaped ；Cur was physically adsorbed in the pores of FL without chemical changes. The bulk density of Cur-FL compound was （0.21±0.02） g/cm3，tap density was （0.33±0.01）g/cm3，angle of repose was（24.07±0.31）°，average particle size was （3.96±0.80） μm，aerodynamic particle size was （3.33±0.99）μm，water content was （5.63 ±0.24）％，emptying rate was （92.53± 0.87）％，and deposition rate of effective parts in vitro was son- （45.93 ± 1.77）％ . Its 24 h solubility in artificial lung gwen.tan@csu.edu.cn fluid [（358.93±1.67）μg/mL] were 3.28 times of Cur ，48 h cumulative release ratesin in vitro （90.21％）were 1.63 times of Cur ，but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid. CONCLUSIONS ：Cur-FL compound powder has good in vitro release property ，and its powder properties ，solubility，water content ，fluidity and aerodynamic properties meet the requirements of DPI in Chinese Pharmacopoeia.