Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.

Protective Mechanism of Icariin on Nephrotic Syndrome Rats Based on RhoA/ROCK Pathway / 中国实验方剂学杂志

Objective:To study the effect of icariin on renin homologous protein A (RhoA)/Rho-related kinase (ROCK) pathway in rats with nephrotic syndrome (NS) and its protective mechanism. Method:Totally 54 clean-grade male SD rats were tested and randomly divided into normal group, model group, RhoA inhibitor group (Rhosin, 40 mg·kg-1·d-1) and three doses of icariin groups (low, medium and high corresponding dose， 30, 60, 120 mg·kg-1·d-1). Adriamycin hydrochloride 6.5 mg·kg-1 was given in tail vein of rats to induce NS model in rats. After the model was established, peritoneal administration was carried out. The normal group and the model group were given saline 2.5 mL·d-1, and the inhibitor group and all of dose groups were given corresponding doses of Rhosin and icariin for intervention. Total urinary protein (Alb), creatinine (Cre), total urinary protein/creatinine ratio (A/C) kit were detected in rats, ultrastructure of kidney was identified by transmission electron microscopy (TEM), and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and proteins expressions of RhoA, ROCK1, ROCK2. Result:TEM showed that the basement membrane was intact and the foot process was regular in the normal group, in model group, basement membrane was damaged seriously, foot process disappeared, and fusion was serious, in the low-dose group, the basement membrane injury was alleviated, the number and density of foot process were improved, and the fusion was obvious， in the middle-dose group and the inhibitor group, the basement membrane thickening was alleviated, and the foot process was slightly fused, in the high-dose group, the basement membrane structure was more complete, and podocytes were longer and arranged tightly. Compared with the normal group, the levels of Alb, Cre and A/C in urine, and RhoA, ROCK1 and ROCK2 mRNA and protein expressions in kidney tissue of rats of the model group were significantly higher (P<0.05). Compared with model group, the levels of Alb, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the inhibitor group and low, medium and high-dose groups, and Cre in urine in inhibitor group and high-dose group decreased significantly (P<0.05). Compared with the inhibitor group, the levels of Alb, Cre in urine and RhoA protein in kidney tissue in the high-dose group were significantly decreased (P<0.05), the levels of Alb, Cre, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue of the low-dose group, and the levels of RhoA, ROCK1 and ROCK2 mRNA expressions in kidney tissue of the middle-dose group were significantly increased (P<0.05). Compared with the low-dose group, the levels of Alb, A/C in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the middle and high-dose groups, Cre in urine of the high-dose group were significantly decreased (P<0.05). Compared with the middle-dose group, the levels of Alb, Cre in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions, ROCK2 mRNA expression in kidney tissue in the high-dose group were significantly decreased (P<0.05). Conclusion:Icariin may protect glomerular endothelium and podocyte by affecting RhoA/ROCK pathway in the treatment of NS rats.

Correlation Study on Pathological Characteristics of Target Organs and Excess Evil Syndrome in IgA Nephropathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy.</p><p><b>METHODS</b>Data were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed.</p><p><b>RESULTS</b>Four syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters.</p><p><b>CONCLUSIONS</b>Excess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.</p>

Treating knee osteoarthritis by Chinese medicine and its correlation study with CT changes of infrapatellar fat pad / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy of Jianbu Tongluo Xunzheng Liquid (JTXL) in treating knee osteoarthritis (KOA), and to explore the correlation between changes of infrapatellar fat pad scanned by CT and the efficacy.</p><p><b>METHODS</b>Totally 105 KOA outpatients were randomly assigned to three groups, i.e., the treatment group, the control group, and the combination group, 35 in each group. Patients in the treatment group were fumigated by JTXL, 30 min each time, once daily, 10 times as a course of treatment, 3 courses in total. Those in the control group received intra-articular injection of Sodium Hyaluronate Injection (SHI), 3 mL each time, once per 6 days, 5 times in total. Those in the combination group were treated by fumigation of JTXL + intra-articular injection of SHI in the same way as the aforesaid two groups. All patients were treated for 30 days. Their clinical efficacy and changes of infrapatellar fat pad scanned by CT were observed, and their correlation was analyzed.</p><p><b>RESULTS</b>The total effective rate was 88.57% in the combination group, better than that of the control group (74.29%) and the treatment group (80.00%; both P < 0.05). Besides, the score for knee joint functions at Hospital for Special Surgery (HSS) was better in the combination group than the other two groups (P < 0.05). The anteroposterior diameter, exterior-interior diameter, the superior-inferior diameter were shortened, and the density decreased in the treatment group and the combination group (P < 0.05). Besides, they were superior to those of the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Changes of infrapatellar fat pad scanned by CT only existed in the combination group and the treatment group, indicating changes of CT scanning was only correlated with effect on changing physicochemical properties of infrapatellar fat pad. Treatment by Chinese medicine could omnipotently and balanced regulate functions and structures of every tissue. Therefore, CT could be taken as a better method for clinical efficacy observation by Chinese medicine.</p>