绿原酸调控HMGB1/TLR4通路对干眼症大鼠角膜炎症的影响OA

Objective To investigate the effects of chlorogenic acid(CA)on corneal inflammation and the high-mobility group box 1(HMGB1)/toll-like receptor 4(TLR4)pathway in rats with dry eye disease(DED).Methods SD rats were induced into DED rat models by injecting scopolamine(12.5 mg·d-1,administered in4 divided doses)onto the surface of the eyeball for 7 consecutive days.Rats were randomly divided into the control group(intraperitoneal injection of physiological saline),DED group(intraperitoneal injection of physiological saline),CA-L group(intraperitoneal injection of 35 mg·kg-1 CA),CA-H group(intraperitoneal injection of 70 mg·kg-1 CA),HMGB1/TLR4 pathway inhibitor group(TAK-242 group)(intraperitoneal injection of 0.25 mg·kg-1 TAK-242),and high-dose CA+HMGB1/TLR4 pathway activator group(CA-H+rRHMGB1 group)(intraperitoneal injection of 70 mg·kg-1 CAand8 μg·kg-1 rRHMGB1),with12 rats in each group.The control group used normal untreated rats,while the other groups used DED model rats.Phenol red cotton thread was used to detect the secretion of the lacrimal gland in rats.Fluorescein staining was used to detect corneal epitheli-al injury in rats.Corneal tissues of rats were collected to detect their pathological changes(hematoxylin-eosin staining),apoptosis of corneal epithelial cells(TUNEL staining),levels of related inflammatory factors(enzyme-linked immunosor-bent assay),positive expression of aquaporin 1(AQP1)and matrix metalloproteinase 9(MMP-9)in corneal tissues(TUNEL staining),and expression levels of HMGB1/TLR4 pathway proteins(Western blot).Results Compared with the control group,mice in the DED group showed corneal tissue damage,inflammatory cell infiltration,and decreased tear secretion and AQP1 protein expression level;however,the corneal fluorescein staining score,corneal epithelial cell apoptosis rate,lev-els of various inflammation related factors,MMP-9 protein expression level,and HMGB1/TLR4 pathway protein expression level in corneal tissues increased.Compared with the DED group,mice the CA-L group,CA-H group,and TAK-242 group showed reduced corneal tissue damage,decreased inflammatory cell infiltration,increased tear secretion and AQP1 protein expression level,and decreased corneal fluorescein staining score,corneal epithelial cell apoptosis rate,levels of various in-flammation related factors,MMP-9 protein expression level,and HMGB1/TLR4 pathway protein expression level in corneal tissues.Compared with the CA-L group,mice in the CA-H group showed reduced corneal tissue damage,decreased inflam-matory cell infiltration,increased tear secretion and AQP1 protein expression level,and decreased corneal fluorescein stai-ning score,corneal epithelial cell apoptosis rate,levels of various inflammation related factors,MMP-9 protein expression level,and HMGB1/TLR4 pathway protein expression level in corneal tissues.Compared with the CA-H group,mice in the CA-H+rRHMGB1 group showed aggravated corneal tissue damage,increased inflammatory cell infiltration,decreased tear secretion and AQP1 protein expression level,and increased corneal fluorescein staining score,corneal epithelial cell apopto-sis rate,levels of various inflammation related factors,MMP-9 protein expression level,and HMGB1/TLR4 pathway protein expression level in corneal tissues,with statistically significant differences(all P<0.05).Conclusion CA can alleviate corneal tissue inflammation and damage in DED rats and improve DED symptoms by inhibiting the HMGB1/TLR4 pathway.