[Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis].

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.

Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-ß-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.