1.Neuroprotective effects of benzatropine on rat model of nonarteritic anterior ischemic optic neuropathy
Linyang GAN ; Jiantao CUI ; Yuyu CHOU ; Yuhan WANG ; Hong DU ; Donghui LI ; Wei DAI ; Hong ZHANG ; Dong ZHANG ; Jin MA ; Yong ZHONG
Chinese Journal of Ocular Fundus Diseases 2019;35(3):259-262
Objective To investigate the neuroprotective effect of Benztropine on retinal ganglion cells (RGCs) death and optic nerve injury in rats model of non-arteritis anterior ischemic optic neuropathy (rNAION).Methods A total of 25 Sprague-Dawley rats were randomly divided into Benztropine treatment group (n=13)and PBS control group (n=12).The right eye was set as the experimental eye.rNAION model was established by using rose Bengal combined with laser photodynamic method.The rats in the Benztropine treatment group were received intraperitoneal injection with Benztropine 10 mg/kg (0.2 ml) daily for 3 weeks,while the rats in the PBS control group were received intraperitoneal injection with an equal volume of PBS.At 1,3 and 7 days after modeling,the retinal and optic disc conditions of the rats were observed by direct ophthalmoscopy.Retrograde labeling,fluorescence microscopy and transmission electron microscopy were used to observe the survival of RGCs and the damage of the optic nerve myelin and axon at 4 weeks after modeling.The RGCs density and survival rate of the two groups were compared by One-Way Anova.Results At 1 and 3 days after modeling,the optic disc edema was observed in the rats of rNAION model group.At 7 days after modeling,the optic disc edema decreased and the boundary was blurred compared with 3 days after modeling.After 4 weeks,the RGCs density in the PBS group was 308± 194/mm2 and the survival rate was 13.7%.The density of RGCs in the Benztropine group was 1173+868/mm2 and the survival rate was 47.6%.The differences of RGCs density and survival rate were significant between the two groups (F=7.552,8.184;P=0.015,0.012).Myelin disintegration,axon degeneration,onion-like body and gliosis were observed in the optic nerve sections of rNIAON in the PBS group,while the damage ofaxon and myelin structure in the Benztropine group was significantly less than that in the PBS group.Conclusions Benztropine group showed higher RGC survival rate,less damage ofaxon and myelin structure on rNAION model.This study explored the potential neuroprotective effect of Benztropine.
2.Improvement effects of Runchang granules on the constipation in mice and its mechanism
Mengqin HUANG ; Xuesong WANG ; Yuhan GAN ; Shiqin LU ; Qiqi DENG ; Qing ZHU ; Jiao GUO
China Pharmacy 2024;35(2):160-165
OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group, model group, Runchang granules low-dose and high-dose groups (5, 10 g/kg), mosapride group (0.003 g/kg, positive control), with 6 mice in each group. The latter 4 groups were given loperamide intragastrically (0.004 g/kg), twice a day, for 3 consecutive days. Normal control group and model group were given purified water intragastrically, and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication, fecal moisture content and intestinal motility of mice were determined, while the structures of colon and ileum, and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor (c-kit), mucin 2 (MUC2) and stem cell factor (SCF) were determined in colon; meanwhile, the mRNA expression levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, inducible nitric oxide synthase (iNOS)] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase (nNOS), smooth muscle myosin light chain kinase (smMLCK), 5-hydroxytryptamine 4 receptor (5-HT4R), MUC2, SCF, c-kit] were determined. RESULTS Compared with model group, the fecal water content, intestinal propulsion rate, protein expression of c-kit in colon, relative expressions of MUC2 and SCF protein, and mRNA expressions of factors related to promoting intestinal motility (except for nNOS and SCF in Runchang granules low-dose group) were all increased significantly in Runchang granules low-dose and high-dose groups, and mosapride group (P<0.05 or P<0.01). mRNA expression levels of inflammatory factors were decreased significantly(P<0.05 or P<0.01). Both colon and ileum injuries improved, and the secretion of colon mucus was increased significantly in Runchang granules high-dose group (P<0.01). CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice, and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression, and the activation of SCF/c-kit signaling pathway.