盐地碱蓬对糖尿病肾脏病大鼠肾脏巨噬细胞凋亡抑制因子及巨噬细胞极化的调控作用

Regulation of Suaeda salsa in renal AIM and macrophage polarization in rats with diabetes kidney disease

目的探讨盐地碱蓬对糖尿病肾脏病(DKD)模型大鼠肾脏巨噬细胞凋亡抑制因子(AIM)及巨噬细胞极化的调控作用。方法采用高糖高脂饮食联合腹腔注射链脲佐菌素(STZ)法建立DKD大鼠模型,将其按随机数字表法分为模型组、二甲双胍组和盐地碱蓬高、中、低剂量组,另设正常组,每组8只。二甲双胍组灌胃二甲双胍溶液85.71 mg/kg,盐地碱蓬高、中、低剂量组灌胃盐地碱蓬混悬液3.08、1.54、0.77 g/kg(生药量),正常组和模型组灌胃等体积生理盐水。1次/d,连续灌胃12周。检测空腹血糖(FBG)、糖耐量(OGTT),并计算曲线下面积;检测血清HbA1c、糖化血清蛋白(GSP)水平;检测血清BUN、SCr及24 h尿蛋白定量(24 hUP);HE染色观察肾脏病理形态;Masson、PAS染色观察肾组织纤维化;Western blot法检测肾组织AIM、CD206、CD86、TNF-α、IL-10蛋白表达;免疫荧光检测肾组织中AIM、甘露糖受体(CD206)、白细胞分化抗原86(CD86)蛋白平均光密度值。结果与模型组比较,盐地碱蓬各剂量组FBG、OGTT曲线下面积、HbA1c、GSP水平降低(P<0.01);肾组织AIM、CD206、IL-10蛋白表达上调(P<0.01或P<0.05),CD86、TNF-α蛋白表达下调(P<0.01或P<0.05),HE、Masson、PAS染色结果显示,与模型组比较,盐地碱蓬各剂量组大鼠肾脏微血管变化及肾脏纤维化情况均得到改善。结论盐地碱蓬可调控AIM、促进M2型巨噬细胞极化、改善巨噬细胞炎症微环境,调节DKD大鼠糖脂代谢、改善肾脏病理损伤。

Objective To explore the regulatory effect of Suaeda salsa on renal apoprosis inhibitor of macrophage(AIM)and macrophage polarization in diabetes kidney disease(DKD)model rats.Methods A DKD rat model was established using a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).The rats were divided into model group,metformin group,and Suaeda salsa high-,medium-,and low-dosage groups using a random number table method,with 8 mice in each group.The normal group was set with 8 rats in this group.The metformin group was given 85.71 mg/kg of metformin solution by gavage,while the Suaeda salsa high-,medium-,and low-dosage groups were given 3.08,1.54,and 0.77 g/kg of Suaeda salsa suspension by gavage(raw dosage).The normal group and model group were given equal volumes of saline by gavage,once a day,administered by gavage for 12 weeks of intervention.Fasting blood glucose(FBG)and glucose tolerance(OGTT)were measured,and the area under the curve(AUC)was calculated;the levels of glycosylated hemoglobin(HbA1c)and glycosylated serum protein(GSP)were detected;urea nitrogen(BUN),serum creatinine(SCr),and 24-hour urine protein(24 hUP)were detected;HE staining was used to observe the pathological morphology of the kidneys;Masson and PAS staining were used to observe renal tissue fibrosis;Western blot method was used for detecting AIM,CD206,CD86,TNF-αand IL-10 protein levels in renal tissue;Immunofluorescence was used to detect the average optical density values of AIM,CD206,and CD86 proteins in renal tissue.Results Compared with the model group,the FBG,OGTT AUC,HbA1c,GSP of each dosage group of Suaeda salsa decreased(P<0.01);the expression levels of AIM,CD206,and IL-10 proteins in renal tissue increased(P<0.01 or P<0.05),while the expression levels of CD86 and TNF-αprotein significantly decreased(P<0.01 or P<0.05);HE,Masson,and PAS staining results showed that compared with the model group,the changes in renal microvasculature and renal fibrosis of rats in each dosage group of Suaeda salsa were improved.Conclusion Suaeda salsa may regulate AIM,promote polarization of M2 macrophages,improve the inflammatory microenvironment of macrophages,thereby lowering blood lipids of DKD rats,and improving renal pathological damage.