ABSTRACT
@#AIM:The dry eye model of rat was induced either by lacrimal gland extirpation or injection of botulinum toxin A into lacrimal gland. The clinical manifestations, pathological features and cytokine changes of these two models were compared, then we discussed their advantages, disadvantages and applicable scope.<p>METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally. The left eye of group A was blank group, group B was the left lacrimal gland extirpation model, the left tear gland of group C was injected with botulinum toxin A. We compared the data of Schirmer I test, tear break-up time(BUT), and the corneal fluoresceince staining scores at different times(1d before experiment, 3d, 7d, 14d, 28d, and 42d after the surgical process). We observed pathological changes of conjunctiva, cornea and lacrimal gland at 42d, and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).<p>RESULTS:At the 3d, compared with group A, the tear secretion of both group B and group C were continuous decrease(<i>P</i><0.05). At the 7d, compared with group A, the BUT of both group B and group C began to decreased(<i>P</i><0.05), and the corneal epithelial staining scores of both group B and group C began to significantly increase(<i>P</i><0.05). There was no statistical difference in the above clinical data between group B and group C(<i>P></i>0.05). The corneal epithelial cells in group A was set as normal morphology, while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees, and the number of conjunctival goblet cells was decreased. The lacrimal gland of group C was obviously atrophic. In conjunctival and corneal tissues, the expression of EGF, TNF-α and IL-6 were significantly increased in group B and group C, which was statistically significant compared with group A(<i>P</i><0.05). The expression of EGF and TNF-α didn't altered significantly between group B and group C(<i>P</i>>0.05), however, the expression of IL-6 in group B was much higher than that in group C(<i>P</i><0.05).<p>CONCLUSION:In this study, we proved that both lacrimal gland extirpation and lacrimal gland injection botulinum toxin A could construct a stable aqueous tear deficiency dry eye rat model. The appropriate animal model should be selected according to the experimental design and research purpose.
ABSTRACT
This study was aimed to explore the effects of tannins in Galla Chinensis on rifampicin in vivo. In the experiment in vitro, UV spectrophotometry and high performance liquid chromatography (HPLC) were used to investigate the solubility of rifampin in pH 1.3, 6.8, artificial gastric juice environment and artificial intestinal fluid environment as well as the effects of tannins on solubility of rifampin in the above conditions. In the experiment in vivo, the process of rifampicin was studied after intragastric administration of rifampicin and rifampicin+ tannins in Galla Chinensis, and then the pharmacokinetic parameters were calculated. The results showed that rifampicin was constantly precipitated in the artificial gastric juice environment over time, and nearly 85% of the rifampicin was precipitated after 6 hours; it showed a good solubility in the artificial intestinal juice environment. After adding the said tannins, the concentration of rifampicin was decreased significantly in both environments, and the concentration of rifampicin in artificial intestinal juice remained relatively stable, while that in artificial gastric juice remained the original downward trend. The pharmacokinetic parameters displayed that as compared with rifampicin alone, AUC0-t and Cmax were decreased significantly, MRT0-t slowed down significantly, Tmax doubled to 7.0 h and the bioavailability was only 31.65% in rifampicin + tannins in Galla Chinensis group. The experiment indicated rifampicin had a poor solubility in acidic environment and the decrease of bioavailability of rifampicin when in combination with tannin was mainly due to the reduction of rifampicin solubility in intestinal tract by complexation of rifampicin with tannin, thus affecting its absorption in intestinal tract. Therefore, rifampicin and the Chinese herbal medicines or Chinese patent medicines rich in tannin should not be taken simultaneously.
Subject(s)
Drugs, Chinese Herbal , Rifampin , Pharmacokinetics , TanninsABSTRACT
Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C₁₈ column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis.