Objective: Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. Methods: Forty male Sprague–Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. Results: TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.001), Cre (z = 3.476; P < 0.001), CysC (z = 4.052; P < 0.001), NGAL (z = 3.661; P < 0.001), and CRP (z = 5.286; P < 0.001) gradually increased after uranium exposure, whereas TAS (z = −3.823; P < 0.001), tissue U (z = −2.736; P = 0.001), Hcy (z = −2.794; P = 0.005), and Lp-PLA2 (z = −4.515; P < 0.001) gradually decreased. The serum U level showed a V-shape change (z = −1.655; P = 0.094). The uranium levels in the kidney tissue and serum were positively correlated with TOS (r = 0.440 and 0.424; P = 0.005 and 0.007) and OSI (r = 0.389 and 0.449; P = 0.013 and 0.004); however, serum U levels were negatively correlated with TAS (r = −0.349; P = 0.027). Partial correlation analysis revealed that NGAL was closely correlated to tissue U (r_partial = 0.455; P = 0.003), CysC was closely correlated to serum U (r_partial = 0.501; P = 0.001), and Lp-PLA2 was closely correlated to TOS (r_partial = 0.391; P = 0.014), TAS (r_partial = 0.569; P < 0.001), and OSI (r_partial = −0.494; P = 0.001). Pearson correlation analysis indicated that the Hcy levels were negatively correlated with tissue U (r = −0.344; P = 0.030) and positively correlated with TAS (r = 0.396; P = 0.011). Conclusion: The uranium-induced oxidative injury may be mainly reflected in enhanced endothelial inflammation, and the direct chemical toxicity of uranium plays an important role in the process of kidney injury, especially in renal tubular injury. In addition, CysC may be a sensitive marker reflecting the nephrotoxicity of uranium; however, Hcy is not suitable for evaluating short-term endothelial inflammation involving oxidative stress.

Yuxuebi tablet (YXB) is a Chinese patent medicine with the effect of activating blood circulation and dissipating blood stasis and has been used to treat "Bi" syndrome in China. The aim of this study was to reveal its anti-inflammatory efficacy and mechanism. A carrageenan-induced inflammation mouse model was established to demonstrate the anti-inflammatory efficacy of YXB by detecting the paw swelling degree and inflammatory cell infiltration in paws. The active chemical ingredients and anti-inflammatory targets of YXB were obtained through network pharmacology analysis. Finally, the core anti-inflammatory targets of YXB were determined by the ELISA method and western blot. YXB significantly reduced the paw swelling degree and inflammatory cell infiltration in paws. A total of 120 key active components included in YXB interacted with 56 core inflammatory targets (such as TNF, IL1B, IL6, PTGS2, RELA, MAPK1, MAPK8, and MAPK14), mainly involving in the TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappaB signaling pathway, and NOD-like receptor signaling pathway. Further studies in vivo found that YXB reduced the levels of TNF-α, IL-1β, and IL-6 in serum and inhibited the expression of COX-2 and the phosphorylation levels of NF-κB p65, JNK, and p38 protein in paws. Taken together, YXB had a good anti-inflammatory effect, which might be related to inhibiting the phosphorylation of NF-κB, JUN, and p38 and the decrease of COX-2 expression and the levels of inflammatory factors.

The effects and relevant mechanisms of Mudan granules in the renal fibrosis of diabetic rats were explored through in vivo experiments, which provided a scientific basis for expanding their clinical indications. Male SD rats were given a single intraperitoneal injection of STZ (65 mg/kg) to induce diabetes rat models. After treatment with Mudan granules, the general condition of rats was recorded. Blood glucose, blood lipids, and renal function-related indicators were detected, renal tissue morphological changes and fibrosis-related indicators were observed, and the expression of pathway-related proteins were examined. The general condition of diabetes rats was improved after the treatment of Mudan granules, the 24-h urinary protein and urinary albumin to creatinine ratio were reduced, and the renal function and lipid results were modified. The tissue damage to the rat kidney has been repaired. Expression of TGF-β1/Smad-related pathway proteins was suppressed in kidney tissues, and the fibrosis factor CO-IV, FN, and LN were reduced in serum. Mudan granules may inhibit of TGF-β1/Smad pathway, inhibit the production of ECM, reduce the levels of fibrosis factors CO-IV, FN, and LN, to have a protective effect on kidney in diabetes rats.