To explore the molecular mechanism of losartan in alleviating renal injury in sepsis.

In animal experiment, mice were randomly divided into the sham group, the model group (modeled by cecal ligation and perforation), losartan group (losartan treatment at 15 mg·kg^-1 after modeling) and antagonist group [treated with the G protein-coupled receptor 84 (GPR84) antagonist GLPG1205 at 30 mg·kg^-1 after modeling], each group contained 10 mice. Enzyme-linked immunosorbent assay (ELISA) experiments were used to detect serum renal injury indicators, and immunohistochemistry was used to detect the protein expressions of GPR84 and cluster of differentiation 86 (CD86) in renal tissues. The expression of cytokines in renal tissues was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). In cell experiment, THP-1 cells were randomly divided into control group, induce group (induced to M1-type macrophages), medicine group (inducing +10 μg·mL^-1 losartan) and medicine+6-OAU group (induction +10 μg·mL^-1 losartan +1 μmol·L^-1 GPR84 antagonist 6-OAU), the relative expression levels of GPR84 protein was detected by Western blot assay, the relative expression level of CD86 was detected by immunofluorescence assay, and the expression of cytokines in cells was detected by RT-qPCR.

In animal experiments, the levels of blood urea nitrogen (BUN) in mice of the sham group, model group, losartan group and antagonist group were (48.55±4.54), (111.28±5.83), (71.52±4.79) and (79.10±8.12) mmol·L^-1, respectively; serum creatinine (SCr) were (13.33±1.58),(64.12±6.91), (30.43±5.80) and (40.09±4.49) μmol·L^-1, respectively; the average optical density values of GPR84 were 0.05±0.01, 0.08±0.01, 0.05±0.01 and 0.05±0.01, respectively; the average optical density values of CD86 were 0.03±0, 0.08±0.01, 0.05±0.01, 0.06±0.01, respectively; the relative expression levels of GPR84 mRNA were 1.00±0.13, 2.70±0.23, 1.78±0.15 and 1.12±0.09, respectively; interleukin (IL)-1β mRNA were 1.00±0.14, 1.78±0.24, 1.41±0.13 and 1.50±0.19, respectively; tumor necrosis factor-alpha (TNF-α) mRNA were 1.00±0.10, 1.85±0.12, 1.39±0.10 and 1.56±0.12, respectively; the relative expression levels of inducible nitric oxide synthase (iNOS) mRNA were 1.00±0.14, 3.33±0.23, 1.93±0.16 and 2.30±0.24, respectively. Compared between the model group and the sham group; compared the losartan group or the contagonist group with the model group and compared between the losartan group with antagonist group, the differences of the above-mentioned indicators were statistically significant (P<0.05, P<0.01, P<0.001). In cell experiments, the relative expression levels of GPR84 protein in the control group, induce group, medicine group and medicine+6-OAU group were 0.58±0.06, 0.94±0.11, 0.63±0.07 and 1.45±0.09, respectively; the fluorescence intensities of CD86 were (1 072.36±105.92), (3 209.59±206.38), (1 903.95±172.73) and (2 471.43±273.18) a.u.; the relative expression levels of iNOS mRNA were 1.00±0.11, 3.06±0.23, 1.98±0.27 and 2.85±0.24, respectively, the above-mentioned indicators compared between the control group and the induce group, compared between the medicine group and the induce group, and compared between the medicine+6-OAU group and the medicine group, the differences were all statistically significant (all P<0.001).

Losartan can alleviate renal injury in sepsis, which is related to the inhibition of GPR84-mediated M1 polarization of macrophages.