Zhongguo quanke yixue (Sep 2022)
Chinese Herbal Formula Shenyi Improves Kidney Injury and Inhibits the Activation of the Alternative Complement Pathway in a Mouse Model of Lupus Nephritis
Abstract
Background Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. Relevant studies have shown that the traditional Chinese herbal formula Shenyi (SY) can regulate the body's immunity and inhibit renal fibrosis. At present, the efficacy and mechanism of using SY in the treatment of LN remains unclear. Objective To explore the therapeutic effect of compound SY on LN mice and the activation of the alternative complement pathway. Methods From April to July 2021, 35 SPF MRL/lpr mice (8 weeks old) and 6 SPF C57BL/6J mice (8 weeks old) were selected for experiments. MRL/lpr mice were randomly divided into MRL/lpr group (n=8) and SY low dose group (n=9) , SY middle dose group (n=9) , SY high dose group (n=9) , C57BL/6J mice were normal control group (n=6) . The low, the medium and high dose groups of SY were respectively administrated with SY decoction at the doses of 15.34, 46.02 and 92.04 g/kg by gavage. The normal control group and MRL/lpr group were respectively administrated with 0.5 ml 0.9 % sodium chloride solution by gavage. Intervention started at 12 weeks of age, once a day for 14 weeks. The animal signs, urinary protein to creatinine ratio (UPCR) , anti-dsDNA antibody (anti-dsDNA) concentration, serum antinuclear antibody (ANA) concentration, renal tissue pathology, renal tissue C3, IgG, C5b-9 immune deposition, renal tissue α-SMA, CollagenⅠ, Fibronectin and complement protein levels were observed. Results At the end of the intervention, 6 mice in normal control group survived, 3 mice in MRL/lpr group survived, and 5, 7 and 9 mice in SY low, the medium and high dose groups survived, respectively. (1) The quantitative scores of the signs of mice in the normal control group, the middle-dose SY group, and the high-dose SY group were lower than those in the MRL/lpr group (P<0.05) . (2) The UPCR in the normal control group and the SY dose groups at the 9th, 10th, 11th, 12th, and 13th weeks of intervention were lower than those in the MRL/lpr group (P<0.05) . (3) The serum anti-dsDNA levels in the normal control group, the low-dose SY group, and the high-dose SY group were lower than those in the MRL/lpr group after 14 weeks of intervention (P<0.05) . After 14 weeks of intervention, the serum ANA levels of mice in the normal control group and SY dose groups were lower than those in the MRL/lpr group (P<0.05) . (4) After 14 weeks of intervention, HE staining showed the deposition of immune complexes in the glomeruli of the MRL/lpr group mice, and PAS staining showed the formation of crescents in the glomeruli. HE staining showed that the glomeruli of mice in each dose group of SY were generally normal, while PAS staining showed that there were mesangial cell proliferation and a small amount of inflammatory cell infiltration in the glomeruli of the mice in the middle and high dose groups of SY. (5) The deposition of C3 and C5b-9 in the kidney tissue of mice in the normal control group and SY dose groups after 14 weeks of intervention was lower than that in the MRL/lpr group (P<0.05) . After 14 weeks of intervention, the IgG immune deposition in renal tissue of low-dose SY group and high-dose SY group was lower than that of MRL/lpr group (P<0.05) . (6) The protein levels of Collagen Ⅰ, Fibronectin, C3, C5, CD35 in kidney tissue of mice in high-dose SY group were lower than those in MRL/lpr group after 14 weeks of intervention (P<0.05) . After 14 weeks of intervention, the protein levels of Fibronectin, C3, C5 and CD35 in renal tissues of low-dose and medium-dose SY groups were lower than those in MRL/ LPR group (P<0.05) . After 14 weeks of intervention, the level of Fibronectin protein in the kidney tissue of mice in the normal control group was lower than that in the MRL/lpr group (P<0.05) . Conclusion SY can ameliorate lupus renal injury in MRL/lpr mice and delay disease progression, and its mechanism of action may be by inhibiting the activation of the alternative complement pathway.
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