| Objective This study explored the therapeutic effect of traditional Chinese medicine Xingbi nasal gel on guinea pigs with allergic rhinitis (AR), and investigated the possible mechanism by inhibiting the activation of the MCs dependent TSLP on nasal mucosa, which aimed to provide experimental and theories basis for the further development and utilization of Xingbi nasal gel, and also provide a new approach to pathogenesis and Traditional Chinese Medicine Prevention for the AR.Methods (1) The AR model of guinea pigs were established by sensitizing with injection of ovalbumin (OVA) together with aluminum hydroxide, and stimulating nasal parts with2%OVA.60guinea pigs were randomly divided into six groups which were normal group, model group, Xingbi Gelation Drop low dose group (6.88mg/kg), middle dose group (13.76mg/kg), high dose group (27.52mg/kg) and budesonide control group (20μg/kg) with10in each group. The ethology of guinea pig in each group was compared.(2) Guinea pigs were intraperitoneal injected with pentobarbital (50mg/kg)1hour after the last excitation, took blood serum, nasal lavage fluid and nasal. The contents of tryptase in blood serum were determined by the method of Lavens SE. The contents of IgE、IL-5、IL-6、 TNF-α、GM-CSF、CCL1、CXCL-8in blood serum and nasal lavage fluid were determined by ELISA. The pathomorphologic changes of Nasal Mucosa’s were observed using HE staining.(3) The protein expression of TSLP、TSLPR and NF-κB in nasal mucosa was detected by immunohistochemistry, and the mRNA expression was detected by RT-PCR.Results (1) The ethology of guinea pig with AR:Typical symptoms were observed with sneezing, scratching nose and runny nose in the model group, and symptoms aggravated along with increase of stimulation frequency. The ethology of guinea pig in the treatment groups were ameliorated significantly compared with model group(P<0.01).The ethology of guinea pig on the fifth stimulation:normal group (1.90±0.74), model group(12.00±1.76), Xingbi Gelation Drop low dose group(8.70±1.34), middle dose group(3.10±0.88), high dose group(2.30±0.95), budesonide control group (2.10±0.31). the AR symptom were markedly improved in the treatment groups(P<0.01).(2) HE staining of Nasal Mucosa’s pathomorphology:The model group experienced a different degree of swelling thickening, vascular dilatation and congestion, increased goblet cells, accompanied by a large number of eosinophils and other inflammatory cell infiltration on the nasal mucosa. EOS count:normal group(1.90±0.74), model group(12.00±1.76), Xingbi Gelation Drop low dose group(8.70±1.34), middle dose group(3.10±0.88), high dose group (2.30±0.95), budesonide control group(2.10±0.31),The eosinophils were significantly reduced in treatment group(P<0.01).(3) Compared with model groups, the level of blood serum tryptase and IgE、IL-5、IL-6、 TNF-α、GM-CSF were markedly decreased(P<0.01or P<0.05)in Xingbi nasal gel middle dose group and high dose group, and in high dose group the content of CXCL-8and CCL-1was significantly reduced (P<0.01or P<0.05). The level ofIL-6、GM-CSF in the Nasal lavage fluid was reduce in Xingbi nasal gel middle dose group and high dose group(P<0.01or P<0.05). The content of IL-5、TNF-α was significantly reduced in high dose group(P<0.01or P<0.05),The level of CXCL-8and CCL-1was reduced in the Nasal lavage fluid, but this was not statistically significant.(4) The results of nasal mucosal immunohistochemistry and RT-PCR:The protein expression of TSLP、TSLPR and NF-κB p65was significantly reduced in Xingbi nasal gel middle dose group and high dose group. The genetic expression of TSLP and NF-κB significantly reduce in Xingbi nasal gel low dose group、middle dose group and high dose group.Conclusion The modern pharmacology experiment we carried on showed that Xingbi nasal gel could alleviate the symptoms of AR in guinea pigs, improve the pathological changes of the nasal mucosa, which suggest that the Xingbi nasal gel has a therapeutic effect on AR, and the mechanism may related to its ability to stabilize mast cells, regulate the of NF-κB signaling to inhibit the release of TSLP, TSLPR and inflammatory factors (IL-5, IL-6, etc.). |
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