Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective:To assess the therapeutic efficacy and histopathological effect of photodynamic therapy (PDT) with intralesional injection of aminolevulinic acid (ALA) in a rat model of acneiform inflammatory nodules.Methods:Forty specific pathogen-free (SPF) SD rats were randomly and equally divided into normal control group, model control group, ALA injection group and topical ALA group. Rats in the normal control group received no treatment, and those in the other 3 groups were inoculated with Propionibacterium acne suspension on the right auricle for the establishment of a rat model of acneiform inflammatory nodules. After successful modeling, rats in the model control group received no other treatment, those in the ALA injection group were intranodularly injected with 5% ALA followed by red light irradiation, and those in the topical ALA group were topically treated with 5% ALA on the acneiform inflammatory nodules followed by red light irradiation. The treatment was performed once a week for 2 weeks. Twenty-four hours after the last treatment, general appearance and histopathological changes of rat ears were observed in each group, the thickness of rat auricles was measured, and liver and kidney functions were evaluated. Statistical analysis was carried out by using one-way analysis of variance and least significant difference- t test for comparisons among the groups. Results:The thickness of rat auricles significantly differed among the normal control group, model control group, topical ALA group and ALA injection group (0.435 ± 0.006, 1.269 ± 0.071, 1.088 ± 0.098, 0.699 ± 0.095 mm, respectively, F = 235.60, P < 0.001) , and was significantly higher in the model control group than in the normal control group, topical ALA group and ALA injection group ( t = 24.18, 5.24, 16.48 respectively, all P < 0.01) , but significantly lower in the ALA injection group than in the topical ALA group ( t = 11.24, P < 0.01) . Compared with the model control group, the topical ALA group and ALA injection group showed decreased degree of local redness and swelling as well as number of nodules on the rat auricle, and decreased quantity of infiltrating inflammatory cells in the dermis and subcutaneous tissues. Compared with the topical ALA group, nodules regressed more markedly in the ALA injection group, and no clumps of inflammatory cells or microabscesses were observed in the ALA injection group. There was no significant difference in levels of alanine aminotransferase, aspartate aminotransferase, creatinine or urea nitrogen among the 4 groups (all P > 0.05) . Conclusion:PDT with intralesional injection of ALA is more effective for the treatment of acneiform inflammatory nodules in rat models than PDT with topical application of ALA.