| Objective: Radiotherapy is one of the most effective treatments for head and neck cancers. However, salivary glands are partially or totally included in the radiation field and caused irreversible xerostomia.The molecular mechanism of radiation-induced xerostomia remain unclear and require further investigation. TNFα and FGF2 are promoting mitosis factor. Numerous studies have shown that fibrosis ofsome tissue is associated with high expression of TNFα and FGF2. The radiation-induced salivary glands damageshowed the destruction of acinar, the normal structure is replaced by fibrous tissue, such as collagen fiber, causing the salivary gland interstitial fibrosis, gland atrophy, reduced volume, etc., which results in the decrease of salivary gland secretion, and even loss. Salivary secretion from the acinar cells was associated with transmembrane transport of various ions, including Cl-、Ca2+、K+、Na+, etc.,Especially transmembrane transport of K+play an important role.Previous studies suggested that mouse submandibular acinar cells express two major K+ channel: Intermediate-Conductance Ca2+-Activated K+ Channels(IK1)and Large-Conductance Ca2+-Activated K+ Channels(BK). The purpose of the firststudy is to explore mechanism of irradiation-induced salivary glands fibrosisbyinvestigatingprotein expression of TNFα and FGF2 after irradiation in rat submandibular gland.The purpose of the second study isto explore mechanism of irradiation-induced salivary glandshypofunction byinvestigatingthe change of IK1 and BK channels electric current after irradiation in rat submandibular gland.Methods: Male Wistar rats, weight 180-220 g, were randomly divided into control group and irradiation group,bilaterally submandibular gland of irradiation group were irradiated with a single dose of 15 Gy.Thecontrol rats were only anesthesia but no irradiated.(1) On the pre-IR, post-IR 3rd day and 30 th day, respectively, the rats bilateral submandibular gland were removed, fixedin4%formaldehydesolution, paraffin-embedded,andsliced,followed the HE staining was used to investigate the histopathology changes and the immunohistochemisty was used to investigatethe expression of TNFα and FGF2 in bilateral submandibular gland of all groups rats.(2)On the pre-IR, post-IR 3rd day,15 th day and 40 th day, respectively, the rats bilateral submandibular gland were removed and disgested in collagenase. A cell with better status was selected from submandibular gland digestive fluid ofeach rat, followed the macroscopic K+ currentschange of IK1 and BK channels in acinar cells of submandibular glandswere recorded with whole-cell patch clamp experiments.Results:(1) Vs the control group, more TNFα and FGF2 were expressed in post-IR 3 days group and post-IR 30 days group rat submandibular gland, and most in the post-radiation 30 days group(all P<0.05,n=5).(2) At +80 m V, vs control group, the current density of BK channel of 3 day group is no significant difference(P>0.05,n=6) and 15 day group reduced 9.7%(p<0.05,n=6) and 40 day group reduced 13.8%(P<0.01,n=6).(3) At +80 m V, vs control group, the current density of IK1 channel of 3 day group is no significant difference(P>0.05,n=6) and 15 day group reduced 12.8%(P<0.05,n=6) and 40 day group reduced 17.1%(P<0.01,n=6).Conclusion:(1) Irradiation can increase the expression of TNFα and FGF2 in rat submandibular gland, which may be one of the reasonsfor radiation-induced salivary glands fibrosis and decrease of salivary gland secretion.(2) Irradiation can reduce the K+ current densities of BK channel and IK1 channelin rat submandibular gland, whichmay be one of the reasonsfor radiation-induced salivary glands hypofunction. |
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