The Effects of Chinese Medicine QRD, Antibiotics, and Probiotics on Therapy and Gut Microbiota in Septic Rats.

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

[Synergistic effect of acupuncture and moxibustion on expression of renal Fas and FasL mRNAs and proteins in contrast-induced nephropathy diabetic rats].

OBJECTIVE: To observe the effect of acupuncture and moxibustion on renal Fas and Fas ligand (FasL) expression in contrast-induced nephropathy (CIN) diabetic rats, so as to explore its protective mechanisms. METHODS: A total of 40 diabetic male SD rats were randomly divided into control, model, acupuncture, moxibustion and combined treatment (acupuncture combined with moxibustion) groups (n＝8 rats in each group). The diabetic model was established by i．p. injection of Streptozotocin (60 mg/kg), followed by regular raising for 9 weeks. Then, the manual acupuncture, moxibustion or acupuncture plus moxibustion at "Sanyinjiao"(SP6) "Shenshu"(BL23) and "Pishu"(BL20) was given to the diabetic rats, once daily for 7 days. On the 8th day, these diabetic rats received i．p. injection of compound Meglumine Diatrizoate Injection (10 mL/kg) for establishing CIN model. Then, the venous blood specimens were collected for detecting contents of serum urine nitrogen (BUN, with urease method) and creatinine (Scr, with picric acid method). The kindey tissues were exteriorized for detecting nitricoxide synthase (NOS, with oxidation-reduction method), malondialdehyde (MDA, with thiobarbituric acid method), superoxide dismutase (SOD, with xanthine oxidase technique) and total antioxidant capacity (T-AOC, with colorimetric technique). The expression levels of Fas and FasL in the kidney tissues were detected by quantitative real-time PCR and Western blot separately. The histopathological and ultrastructural changes of the kidney were observed under microscope (after H．E. staining) and transmission electron microscope, respectively. RESULTS: Following modeling and compared with the control group, the BUN, Scr and renal MDA contents, and Fas and FasL mRNA and protein expression levels were significantly increased (P<0.01, P<0.05), and renal NOS, SOD and T-AOC levels considerably decreased in the model group (P<0.05). After the interventions and compared with the model group, serum BUN and Scr contents and renal Fas mRNA and protein expression levels in both acupuncture group and combined treatment group, BUN in the moxibustion group, and renal MDA content and FasL mRNA and protein expression levels in the 3 treatment groups were obviously down-regulated (P<0.05，P<0.01), while renal NOS in the 3 treatment groups, and SOD and T-AOC levels in the combined treatment group were considerably up-regulated (P<0.01，P<0.05). The effects of the combined treatment were significantly superior to those of simple acupuncure and simple moxibustion in down-regulating serum BUN contents, and Fas and FasL mRNA and protein expression levels, and in up-regulating renal NOS, SOD and T-AOC activity (P<0.05). No significant differences were found between the acupuncture and moxibustion groups in down-regulating serum BUN, Scr and renal MDA contents, and Fas and FasL mRNA and protein levels, as well as in up-regulating NOS content (P>0.05). H．E. staining showed lobular changes of glomeruli, many local necrosis and vascular degeneration in the model group, and transmission electron microscope displayed thickened basement membrane of the glomerular blood loop, many vacuoles in the cytoplasm of renal tubular epithelial cells, severely swollen mitochondria with disordered, broken or disappeared cristae, and some apoptotic cells in the model group, which were relatively milder in the combined treatment group. CONCLUSION: Joint application of acupuncture and moxibustion can reduce the oxidative stress and renal injury in CIN diabetic rats, which may be associated with its function in down-regulating the expression of renal Fas and FasL genes and proteins. Acupuncture and moxibustion has a synergistic effect.

Cordyceps sinensis prevents contrast-induced nephropathy in diabetic rats: its underlying mechanism.

Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). This study investigated the renal protective effect of cordyceps sinensis (CS) in a diabetic rat model of CIN and the mechanism of its effect. Sixty SD rats were randomly divided into 4 groups, the control group, model group, probucol group, and CS group. We used a diabetic rat model of Iodixanol-induced CIN. Serum creatinine (Scr), blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL) levels were measured to evaluate renal function. Total antioxidative ability (T-AOC), superoxide dismutase (SOD), and malonaldehyde (MDA) levels were assessed to discuss the effect of probucol and CS on oxidative stress. The pathologic changes in the kidney were observed by hematoxylin and eosin (HE) staining and periodic acid-Schiff (PAS) staining. Apoptosis was assessed by transmission electron microscopy and TUNEL staining. Caspase-3, Bax, Bcl2 and phospho-p38 mitogen-activated protein kinase (MAPK) protein expressions were assessed by Western blotting. The model group of rats showed significantly elevated levels of BUN, Scr, urinary KIM-1, NGAL, and parameters of oxidative stress (P<0.05). Both the probucol and CS groups demonstrated significantly lower Scr, BUN, and urinary KIM-1, NGAL levels compared to the model group (P<0.05), with no significant difference between these two groups. The probucol group and the CS group had significantly lower MDA and higher T-AOC, SOD than the model group after modeling (P<0.05). Caspase-3, Bax activation were effectively repressed while Bcl-2 expression was increased by probucol and CS pretreatment. Mechanistically, probucol and CS decreased the expression of JNK protein and increased the expression of ERK protein. CS can effectively reduce kidney damage caused by contrast medium. The underlying mechanism may be that CS accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress and influencing MAPK signal pathways.