Page 102 - 2022-26-中国全科医学

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Liberation Army/State Key Laboratory of Kidney Diseases/National Clinical Research Center for Kidney Diseases/Beijing Key
Laboratory of Kidney Disease Research，Beijing 100853，China
3.Department of Nephrology，Guizhou Provincial People's Hospital，Guiyang 550002，China
*
Corresponding author：CHEN Xiangmei，Professor；E-mail：xmchen301@126.com
【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，Collagen Ⅰ，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.
【Key words】 Lupus nephritis；Shenyi；Renal agents （TCD）；Drugs，Chinese herbal；Complement；MRL/lpr mice

狼疮肾炎（LN）是系统性红斑狼疮（SLE）严重 剂治疗常伴有严重的并发症，如感染、心血管疾病、骨
且常见的并发症之一 ［1］ 。研究表明，LN 的发病机制 质疏松症等 ［5-7］ 。中药复方肾怡（SY）是中国人民解
与补体的激活相关 ［2-3］ 。多项临床数据研究显示， 放军总医院肾脏病科的自拟方剂，原方为莲慈汤 ［8］ ，
7%~31% 的 SLE 患者在 SLE 初次诊断时即被诊断为 由白术、败酱草、半边莲、补骨脂、黄连、女贞子、三
LN，31%~48% 的 SLE 患者在随访期间被诊断为 LN， 棱、王不留行等药物组成，药物主要归肾、肝、脾经，
［4］
4%~28% 的 LN 患者最终进展为终末期肾病（ESRD） 。 处方功效为活血化瘀、补肾滋阴、清热解毒、利水消肿。
临床上 SLE 与 LN 的治疗主要以免疫抑制剂与激素为主， 前期研究显示复方 SY 可以通过影响 MRL/lpr 小鼠体内
+
但无论是单纯激素治疗还是免疫抑制剂治疗抑或联合治 CD 4 T 淋巴细胞分化，纠正肾脏组织中的辅助性 T（Th）
疗方案，均仅对部分患者有效，且激素治疗和免疫抑制 1/Th2 细胞的比例失衡，从而改善动物的肾脏损害 ［9-10］ 。