The Effect Of18β-Glycyrrhetinic Acid On The Endoplasmic Reticulum Of Nasal Epithelial Cells In Rat Models Of Allergic Rhinitis And On Normal Rat Kidney

18(3-glycyrrhetinic acid (18β-GA), a metabolite of glycyrrhiza extract, is widely used due to its good physiological activity, biological compatibility and lower adverse reaction. The existing research showed that18β-GA had the functions of immunoregulation, anti-inflammation and parahormone. Allergic rhinitis (AR) is a kind of nasal mucosa allergic disease mediated by IgE. The pathogenesis belongs to type1hypersensitivity, which is closely related to cytokine, intercellular adhesion molecule (ICAM) and parts of the neuropeptides. The process of pathogenesis involves the activation of T-and B-cells, the synthesis of cytokines (such as interleukin and tumor necrosis factor etc.) and the release of inflammatory mediator. As with mitochondria, the endoplasmic reticulum is considered to have a central role in cell’s vital movement, with the morphological structure changes reflecting the changes of cell’s functions. However, during the application of glycyrrhetinic acid, its side effect will also appear gradually. The kidney acts as the important organ for drug metabolism, and its functional morphology can reflect the toxic and side effect of drug to some extent. The botany species of herbal medicine are the fundamental factors to led renal damage, which is related to the dosage, usage and treatment duration. The reports on the side effect of glycyrrhetinic acid mainly include the functions of adrenocorticomimetic produced by long-period or large doses of glycyrrhizic acid. However, there are few reports on the influence of large dose and long-period gastric perfusion of glycyrrhetinic acid on the rat’s renal pathological morphology, renal function and biochemical index. In this study,18β-glycyrrhetinic acid is fed to the model rat with allergic rhinitis, and then observes the morphologic change of endoplasmic reticulum of nasal mucous epithelial cell from mat, which will objectively reflect the effect on the endoplasmic reticulum of nasal mucous epithelial cell from mat with allergic rhinitis. At the same time, the influence on the pathomorphology and biochemical indicators of renal function shall be observed after long-period or large dose gastric perfusion of glycyrrhetinic acid on rat, which will provide experiment support for pharmacological mechanism of glycyrrhetinic acid. Part one:The Effect of18β-Glycyrrhetinic Acid on the Endoplasmic Reticulum of Nasal Epithelial Cells in Rat Models of Allergic RhinitisObjective:To study the effect of18β-glycyrrhetinic acid on the endoplasmic reticulum of nasal epithelial cells in rat model with allergic rhinitis.Methods:One hundred and twenty Wistar rats were randomly divided into blank group, AR model group, loratadine group and glycyrrhetinic acid group, AR models were established by ovalbumin(OVA) and each group were treated respectively. The ultrastructure of the endoplasmic reticulum was observed at the second, fourth, sixth and tenth week after drug intervention.Results:Compared with blank group, the endoplasmic reticulum in number in AR model group increased, accompanying with a significant cystic dilatation, a lot of vacuole formation, degranulation and a large number of free ribosomes in cytoplasm. With persistent allergen exposure, the changes mentioned above in the endoplasmic reticulum of mucous epithelium in the AR modal group was getting worse. Meanwhile, the dilation of endoplasmic reticulum, vacuole formation and degranulation in glycyrrhetinic acid group was improved and getting close to the blank group with the extension of the observation comparing with AR model.Conclusion:18(3-Glycyrrhetinic acid can improve the expansion, vacuolization and degranulation of the endoplasmic reticulum of nasal epithelial cells in rat model of allergic rhinitis. Part two:Influence of18β-glycyrrhetinic Acid on Normal Rat KidneyObjective:To study on the influence of18β-glycyrrhetinic acid (GA) on normal rat kidney.Methods:120Wistar rats were divided into four groups, including blank control group, low-dose GA group, medium GA group, and high GA group. Blood collection from cardiac puncture was conducted at the sixth, fourteenth, twenty-second, thirtieth week and at the time with GA withdrawal for four weeks after intervention with glycyrrhetinic acid, and took the kidney for inspection at the same time.Results:With the intervention was processed until4-week drug withdrawal, low-does, medium-does and high-does GA groups compared with blank control group, there was no Statistical significance among serum creatinine (CREA) and blood urea nitrogen (BUN). Compared with blank control group, serum sodium and chloride ions increased. However, after4-week drug withdrawal, serum sodium and chloride ions decreased compared with the ones at previous weeks, which got close to blank control group. Compared with blank control group, serum potassium ions decreased. After4-week drug withdrawal, serum potassium ions increased compared with the ones at each time point, getting close to blank control group. Each time, The above indicators was no statistical difference between the low-does, medium-doses and high-doses of GA group. Compared with blank control group, no abnormal change was found in kidney pathological morphology at each time point by HE dyeing method.Conclusions:18β-glycyrrhetinic acid had no significant effect on rats’ blood urea nitrogen, creatinine value and kidney pathological morphology. It can cause the mild elevation of serum sodium and chloride ions and the decrease of serum potassium ions. The influence can be eliminated after drug withdrawal.