Liang Wen-Jie, Ma Xue-Lian, Wang Xuan, Xiong Yun-Zhao, Wang Xiang-Ting, Xu Qing-You
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2017 Apr;37(4):470-475.
Objective To observe the effect of Huayu Jiedu Recipe (HJR) on the expressions of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) , Caspase-1 , IL-1 β in kidneys of obstructive nephropathy rats. Methods Totally 40 clean grade SD rats were randomly divided into the sham-operation group (n =10) and the model group (n =30). The model of obstructive nephropa- thy was established by unilateral ureteral obstruction (UUO). Totally 30 successfully modeled UUO rats were randomly divided into the model group, the Western medicine group, the Chinese medicine group, 10 in each group. Eplerenone (100 mg . kg ⁻¹ . d⁻¹) was administrated to rats in the Western medicine group. HJR (13.7 g . kg ⁻¹ . d⁻¹) was administrated to rats in the Chinese medicine group. Equal volume of normal saline was administered to rats in the sham-operation group and the model group. All medica- tion was performed once daily for 10 successive days. The serum IL-1 β level was detected. Protein and mRNA expressions of NLRP3, Caspase-1, and IL-1 β in renal tissue were detected. TUNEL positive rate was detected by TUNEL method. Results The expression of NLRP3 was not obviously seen, Caspase-1 and IL-1 β were weakly expressed, and only fewer amount of TUNEL positive cells could be seen in the sham-operation group. Compared with the sham-operation group, serum IL-1β level increased (P < 0. 01) , mRNA and protein expression of NLRP3, Caspase-1 , and IL-1 β were up-regulated in renal tissue of the model group (P <0. 01). NLRP3 was mainly expressed in renal interstitial macrophages and renal tubular epithelial cells. Caspase-1 and IL-1 β were mainly expressed in the cytoplasm of renal tubular epithelial cells. TUNEL positive cells were significantly increased, mainly dominated in interstitial expanded epithelial cells of distal tubules (P <0. 01). Compared with the model group, serum IL-1 β level was significantly decreased (P <0. 01) ; mRNA and protein expressions of NLRP3, Caspase-1 , and IL- β were obviously down-regulated (P <0. 01) , and the TUNEL positive rate was obviously decreased (P <0. 05, P < 0. 01) in the two medicated groups. Conclusion HJR could down-regulate mRNA and protein expres- sions of NLRP3, Caspase-1 , and IL-1β, thus attenuating inflammatory injury of renal tissue.
目的 观察化瘀解毒方（HJR）对梗阻性肾病大鼠肾脏中核苷酸结合寡聚化结构域（NOD）样受体蛋白3（NLRP3）、半胱天冬酶-1（Caspase-1）、白细胞介素-1β（IL-1β）表达的影响。方法 将40只清洁级SD大鼠随机分为假手术组（n =10）和模型组（n =30）。采用单侧输尿管梗阻（UUO）法建立梗阻性肾病模型。将30只成功造模的UUO大鼠随机分为模型组、西药组、中药组，每组10只。西药组大鼠给予依普利酮（100 mg·kg⁻¹·d⁻¹），中药组大鼠给予HJR（13.7 g·kg⁻¹·d⁻¹），假手术组和模型组大鼠给予等体积的生理盐水。所有给药均每日1次，连续给药10天。检测血清IL-1β水平，检测肾组织中NLRP3、Caspase-1、IL-1β的蛋白和mRNA表达，采用TUNEL法检测TUNEL阳性率。结果 假手术组未见明显的NLRP3表达，Caspase-1和IL-1β呈弱表达，仅见少量TUNEL阳性细胞。与假手术组比较，模型组大鼠血清IL-1β水平升高（P <0.01），肾组织中NLRP3、Caspase-1、IL-1β的mRNA和蛋白表达上调（P <0.01）。NLRP3主要表达于肾间质巨噬细胞和肾小管上皮细胞，Caspase-1和IL-1β主要表达于肾小管上皮细胞的胞质中。TUNEL阳性细胞显著增多，主要集中于远端肾小管间质扩张的上皮细胞（P <0.01）。与模型组比较，两个给药组大鼠血清IL-1β水平显著降低（P <0.01）；NLRP3、Caspase-1、IL-1β的mRNA和蛋白表达明显下调（P <0.01），TUNEL阳性率明显降低（P <0.05，P <0.01）。结论 HJR可下调NLRP3、Caspase-1、IL-1β的mRNA和蛋白表达，从而减轻肾组织的炎性损伤。
